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+anno_start	anno_end	anno_text	entity_type	sentence	section
+0	9	Structure	evidence	Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf	TITLE
+27	30	Wnt	protein_type	Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf	TITLE
+41	48	Kremen1	protein	Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf	TITLE
+97	101	LRP6	protein	Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf	TITLE
+106	114	Dickkopf	protein_type	Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf	TITLE
+0	14	Kremen 1 and 2	protein_type	Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling.	ABSTRACT
+39	51	co-receptors	protein_type	Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling.	ABSTRACT
+56	64	Dickkopf	protein_type	Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling.	ABSTRACT
+66	69	Dkk	protein_type	Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling.	ABSTRACT
+124	127	Wnt	protein_type	Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling.	ABSTRACT
+22	40	crystal structures	evidence	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+48	58	ectodomain	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+62	67	human	species	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+68	75	Kremen1	protein	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+77	81	KRM1	protein	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+81	84	ECD	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+124	128	KRM1	protein	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+128	131	ECD	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+198	220	triangular arrangement	protein_state	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+228	235	Kringle	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+237	240	WSC	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+246	249	CUB	structure_element	We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains.	ABSTRACT
+4	14	structures	evidence	The structures reveal an unpredicted homology of the WSC domain to hepatocyte growth factor.	ABSTRACT
+53	56	WSC	structure_element	The structures reveal an unpredicted homology of the WSC domain to hepatocyte growth factor.	ABSTRACT
+67	91	hepatocyte growth factor	protein_type	The structures reveal an unpredicted homology of the WSC domain to hepatocyte growth factor.	ABSTRACT
+80	83	Wnt	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+84	95	co-receptor	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+96	102	Lrp5/6	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+104	107	Dkk	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+113	116	Krm	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+159	176	crystal structure	evidence	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+185	221	β-propeller/EGF repeats (PE) 3 and 4	structure_element	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+229	232	Wnt	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+233	244	co-receptor	protein_type	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+245	249	LRP6	protein	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+251	255	LRP6	protein	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+255	261	PE3PE4	structure_element	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+268	290	cysteine-rich domain 2	structure_element	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+292	296	CRD2	structure_element	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+301	305	DKK1	protein	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+311	315	KRM1	protein	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+315	318	ECD	structure_element	We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD.	ABSTRACT
+0	4	DKK1	protein	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+4	8	CRD2	structure_element	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+31	35	LRP6	protein	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+35	38	PE3	structure_element	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+43	47	KRM1	protein	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+47	58	Kringle-WSC	structure_element	DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC.	ABSTRACT
+0	8	Modeling	experimental_method	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+30	55	surface plasmon resonance	experimental_method	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+73	89	interaction site	site	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+98	102	Krm1	protein	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+102	105	CUB	structure_element	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+110	114	Lrp6	protein	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+114	117	PE2	structure_element	Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.	ABSTRACT
+4	13	structure	evidence	The structure of the KREMEN 1 ectodomain is solved from three crystal forms	ABSTRACT
+21	29	KREMEN 1	protein	The structure of the KREMEN 1 ectodomain is solved from three crystal forms	ABSTRACT
+30	40	ectodomain	structure_element	The structure of the KREMEN 1 ectodomain is solved from three crystal forms	ABSTRACT
+44	50	solved	experimental_method	The structure of the KREMEN 1 ectodomain is solved from three crystal forms	ABSTRACT
+62	75	crystal forms	evidence	The structure of the KREMEN 1 ectodomain is solved from three crystal forms	ABSTRACT
+0	7	Kringle	structure_element	Kringle, WSC, and CUB subdomains interact tightly to form a single structural unit	ABSTRACT
+9	12	WSC	structure_element	Kringle, WSC, and CUB subdomains interact tightly to form a single structural unit	ABSTRACT
+18	21	CUB	structure_element	Kringle, WSC, and CUB subdomains interact tightly to form a single structural unit	ABSTRACT
+4	13	interface	site	The interface to DKKs is formed from the Kringle and WSC domains	ABSTRACT
+17	21	DKKs	protein_type	The interface to DKKs is formed from the Kringle and WSC domains	ABSTRACT
+41	48	Kringle	structure_element	The interface to DKKs is formed from the Kringle and WSC domains	ABSTRACT
+53	56	WSC	structure_element	The interface to DKKs is formed from the Kringle and WSC domains	ABSTRACT
+4	7	CUB	structure_element	The CUB domain is found to interact directly with LRP6PE1PE2	ABSTRACT
+50	54	LRP6	protein	The CUB domain is found to interact directly with LRP6PE1PE2	ABSTRACT
+54	60	PE1PE2	structure_element	The CUB domain is found to interact directly with LRP6PE1PE2	ABSTRACT
+28	38	ectodomain	structure_element	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+39	48	structure	evidence	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+52	60	KREMEN 1	protein	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+64	72	receptor	protein_type	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+77	80	Wnt	protein_type	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+100	103	DKK	protein_type	Zebisch et al. describe the ectodomain structure of KREMEN 1, a receptor for Wnt antagonists of the DKK family.	ABSTRACT
+0	3	Apo	protein_state	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+4	14	structures	evidence	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+21	33	complex with	protein_state	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+34	54	functional fragments	protein_state	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+58	62	DKK1	protein	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+67	71	LRP6	protein	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+130	133	Wnt	protein_type	Apo structures and a complex with functional fragments of DKK1 and LRP6 shed light on the function of this dual-mode regulator of Wnt signaling.	ABSTRACT
+13	16	Wnt	protein_type	Signaling by Wnt morphogens is renowned for its fundamental roles in embryonic development, tissue homeostasis, and stem cell maintenance.	INTRO
+68	71	Wnt	protein_type	Due to these functions, generation, delivery, and interpretation of Wnt signals are all heavily regulated in the animal body.	INTRO
+0	10	Vertebrate	taxonomy_domain	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+11	19	Dickkopf	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+30	34	Dkk1	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+36	37	2	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+43	44	4	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+86	89	Wnt	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+129	132	Wnt	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+133	144	co-receptor	protein_type	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+145	151	LRP5/6	protein	Vertebrate Dickkopf proteins (Dkk1, 2, and 4) are one of many secreted antagonists of Wnt and function by blocking access to the Wnt co-receptor LRP5/6.	INTRO
+0	6	Kremen	protein_type	Kremen proteins (Krm1 and Krm2) have been identified as additional high-affinity transmembrane receptors for Dkk.	INTRO
+17	21	Krm1	protein_type	Kremen proteins (Krm1 and Krm2) have been identified as additional high-affinity transmembrane receptors for Dkk.	INTRO
+26	30	Krm2	protein_type	Kremen proteins (Krm1 and Krm2) have been identified as additional high-affinity transmembrane receptors for Dkk.	INTRO
+81	104	transmembrane receptors	protein_type	Kremen proteins (Krm1 and Krm2) have been identified as additional high-affinity transmembrane receptors for Dkk.	INTRO
+109	112	Dkk	protein_type	Kremen proteins (Krm1 and Krm2) have been identified as additional high-affinity transmembrane receptors for Dkk.	INTRO
+0	3	Krm	protein_type	Krm and Dkk synergize in Wnt inhibition during Xenopus embryogenesis to regulate anterior-posterior patterning.	INTRO
+8	11	Dkk	protein_type	Krm and Dkk synergize in Wnt inhibition during Xenopus embryogenesis to regulate anterior-posterior patterning.	INTRO
+25	28	Wnt	protein_type	Krm and Dkk synergize in Wnt inhibition during Xenopus embryogenesis to regulate anterior-posterior patterning.	INTRO
+47	54	Xenopus	taxonomy_domain	Krm and Dkk synergize in Wnt inhibition during Xenopus embryogenesis to regulate anterior-posterior patterning.	INTRO
+43	54	presence of	protein_state	Mechanistically it is thought that, in the presence of Dkk, Krm forms a ternary complex with Lrp6, which is then rapidly endocytosed.	INTRO
+55	58	Dkk	protein_type	Mechanistically it is thought that, in the presence of Dkk, Krm forms a ternary complex with Lrp6, which is then rapidly endocytosed.	INTRO
+60	63	Krm	protein_type	Mechanistically it is thought that, in the presence of Dkk, Krm forms a ternary complex with Lrp6, which is then rapidly endocytosed.	INTRO
+80	92	complex with	protein_state	Mechanistically it is thought that, in the presence of Dkk, Krm forms a ternary complex with Lrp6, which is then rapidly endocytosed.	INTRO
+93	97	Lrp6	protein_type	Mechanistically it is thought that, in the presence of Dkk, Krm forms a ternary complex with Lrp6, which is then rapidly endocytosed.	INTRO
+29	32	Wnt	protein_type	This amplifies the intrinsic Wnt antagonistic activity of Dkk by efficiently depleting the cell surface of the Wnt co-receptor.	INTRO
+58	61	Dkk	protein_type	This amplifies the intrinsic Wnt antagonistic activity of Dkk by efficiently depleting the cell surface of the Wnt co-receptor.	INTRO
+111	114	Wnt	protein_type	This amplifies the intrinsic Wnt antagonistic activity of Dkk by efficiently depleting the cell surface of the Wnt co-receptor.	INTRO
+115	126	co-receptor	protein_type	This amplifies the intrinsic Wnt antagonistic activity of Dkk by efficiently depleting the cell surface of the Wnt co-receptor.	INTRO
+25	29	Krm1	protein_type	In accordance with this, Krm1−/− and Krm2−/− double knockout mice show a high bone mass phenotype typical of increased Wnt signaling, as well as growth of ectopic forelimb digits.	INTRO
+37	41	Krm2	protein_type	In accordance with this, Krm1−/− and Krm2−/− double knockout mice show a high bone mass phenotype typical of increased Wnt signaling, as well as growth of ectopic forelimb digits.	INTRO
+45	60	double knockout	experimental_method	In accordance with this, Krm1−/− and Krm2−/− double knockout mice show a high bone mass phenotype typical of increased Wnt signaling, as well as growth of ectopic forelimb digits.	INTRO
+61	65	mice	taxonomy_domain	In accordance with this, Krm1−/− and Krm2−/− double knockout mice show a high bone mass phenotype typical of increased Wnt signaling, as well as growth of ectopic forelimb digits.	INTRO
+119	122	Wnt	protein_type	In accordance with this, Krm1−/− and Krm2−/− double knockout mice show a high bone mass phenotype typical of increased Wnt signaling, as well as growth of ectopic forelimb digits.	INTRO
+69	72	dkk	protein_type	Growth of ectopic digits is further enhanced upon additional loss of dkk expression.	INTRO
+4	7	Wnt	protein_type	The Wnt antagonistic activity of Krm1 is also linked to its importance for correct thymus epithelium formation in mice.	INTRO
+33	37	Krm1	protein_type	The Wnt antagonistic activity of Krm1 is also linked to its importance for correct thymus epithelium formation in mice.	INTRO
+114	118	mice	taxonomy_domain	The Wnt antagonistic activity of Krm1 is also linked to its importance for correct thymus epithelium formation in mice.	INTRO
+18	24	intact	protein_state	The importance of intact KRM1 for normal human development and health is highlighted by the recent finding that a homozygous mutation in the ectodomain of KRM1 leads to severe ectodermal dysplasia including oligodontia.	INTRO
+25	29	KRM1	protein	The importance of intact KRM1 for normal human development and health is highlighted by the recent finding that a homozygous mutation in the ectodomain of KRM1 leads to severe ectodermal dysplasia including oligodontia.	INTRO
+41	46	human	species	The importance of intact KRM1 for normal human development and health is highlighted by the recent finding that a homozygous mutation in the ectodomain of KRM1 leads to severe ectodermal dysplasia including oligodontia.	INTRO
+141	151	ectodomain	structure_element	The importance of intact KRM1 for normal human development and health is highlighted by the recent finding that a homozygous mutation in the ectodomain of KRM1 leads to severe ectodermal dysplasia including oligodontia.	INTRO
+155	159	KRM1	protein	The importance of intact KRM1 for normal human development and health is highlighted by the recent finding that a homozygous mutation in the ectodomain of KRM1 leads to severe ectodermal dysplasia including oligodontia.	INTRO
+19	22	Wnt	protein_type	Interestingly, the Wnt antagonistic activity of Krm is context dependent, and Krm proteins are actually dual-mode Wnt regulators.	INTRO
+48	51	Krm	protein_type	Interestingly, the Wnt antagonistic activity of Krm is context dependent, and Krm proteins are actually dual-mode Wnt regulators.	INTRO
+78	81	Krm	protein_type	Interestingly, the Wnt antagonistic activity of Krm is context dependent, and Krm proteins are actually dual-mode Wnt regulators.	INTRO
+114	117	Wnt	protein_type	Interestingly, the Wnt antagonistic activity of Krm is context dependent, and Krm proteins are actually dual-mode Wnt regulators.	INTRO
+7	17	absence of	protein_state	In the absence of Dkk, Krm1 and 2 change their function from inhibition to enhancement of Lrp6-mediated signaling.	INTRO
+18	21	Dkk	protein_type	In the absence of Dkk, Krm1 and 2 change their function from inhibition to enhancement of Lrp6-mediated signaling.	INTRO
+23	27	Krm1	protein_type	In the absence of Dkk, Krm1 and 2 change their function from inhibition to enhancement of Lrp6-mediated signaling.	INTRO
+32	33	2	protein_type	In the absence of Dkk, Krm1 and 2 change their function from inhibition to enhancement of Lrp6-mediated signaling.	INTRO
+90	94	Lrp6	protein_type	In the absence of Dkk, Krm1 and 2 change their function from inhibition to enhancement of Lrp6-mediated signaling.	INTRO
+21	25	Lrp6	protein_type	By direct binding to Lrp6 via the ectodomains, Krm proteins promote Lrp6 cell-surface localization and hence increase receptor availability.	INTRO
+34	45	ectodomains	structure_element	By direct binding to Lrp6 via the ectodomains, Krm proteins promote Lrp6 cell-surface localization and hence increase receptor availability.	INTRO
+47	50	Krm	protein_type	By direct binding to Lrp6 via the ectodomains, Krm proteins promote Lrp6 cell-surface localization and hence increase receptor availability.	INTRO
+68	72	Lrp6	protein_type	By direct binding to Lrp6 via the ectodomains, Krm proteins promote Lrp6 cell-surface localization and hence increase receptor availability.	INTRO
+37	40	Krm	protein_type	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+83	87	Krm1	protein_type	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+97	101	Krm2	protein_type	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+133	139	LRP5/6	protein	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+144	147	Wnt	protein_type	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+202	210	bound to	protein_state	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+211	214	Dkk	protein_type	Further increasing the complexity of Krm functionality, it was recently found that Krm1 (but not Krm2) can also act independently of LRP5/6 and Wnt as a dependence receptor, triggering apoptosis unless bound to Dkk.	INTRO
+14	18	Krm1	protein_type	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+23	24	2	protein_type	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+29	58	type I transmembrane proteins	protein_type	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+73	83	ectodomain	structure_element	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+90	98	flexible	protein_state	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+99	115	cytoplasmic tail	structure_element	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+130	132	60	residue_range	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+133	135	75	residue_range	Structurally, Krm1 and 2 are type I transmembrane proteins with a 40 kDa ectodomain and a flexible cytoplasmic tail consisting of 60–75 residues.	INTRO
+4	14	ectodomain	structure_element	The ectodomain consists of three similarly sized structural domains of around 10 kDa each: the N-terminal Kringle domain (KR) is followed by a WSC domain of unknown fold.	INTRO
+106	113	Kringle	structure_element	The ectodomain consists of three similarly sized structural domains of around 10 kDa each: the N-terminal Kringle domain (KR) is followed by a WSC domain of unknown fold.	INTRO
+122	124	KR	structure_element	The ectodomain consists of three similarly sized structural domains of around 10 kDa each: the N-terminal Kringle domain (KR) is followed by a WSC domain of unknown fold.	INTRO
+143	146	WSC	structure_element	The ectodomain consists of three similarly sized structural domains of around 10 kDa each: the N-terminal Kringle domain (KR) is followed by a WSC domain of unknown fold.	INTRO
+33	36	CUB	structure_element	The third structural domain is a CUB domain.	INTRO
+3	27	approximately 70-residue	residue_range	An approximately 70-residue linker connects the CUB domain to the transmembrane span.	INTRO
+28	34	linker	structure_element	An approximately 70-residue linker connects the CUB domain to the transmembrane span.	INTRO
+48	51	CUB	structure_element	An approximately 70-residue linker connects the CUB domain to the transmembrane span.	INTRO
+66	84	transmembrane span	structure_element	An approximately 70-residue linker connects the CUB domain to the transmembrane span.	INTRO
+3	9	intact	protein_state	An intact KR-WSC-CUB domain triplet and membrane attachment is required for Wnt antagonism.	INTRO
+10	20	KR-WSC-CUB	structure_element	An intact KR-WSC-CUB domain triplet and membrane attachment is required for Wnt antagonism.	INTRO
+76	79	Wnt	protein_type	An intact KR-WSC-CUB domain triplet and membrane attachment is required for Wnt antagonism.	INTRO
+4	22	transmembrane span	structure_element	The transmembrane span and cytoplasmic tail can be replaced with a GPI linker without impact on Wnt antagonism.	INTRO
+27	43	cytoplasmic tail	structure_element	The transmembrane span and cytoplasmic tail can be replaced with a GPI linker without impact on Wnt antagonism.	INTRO
+67	70	GPI	structure_element	The transmembrane span and cytoplasmic tail can be replaced with a GPI linker without impact on Wnt antagonism.	INTRO
+71	77	linker	structure_element	The transmembrane span and cytoplasmic tail can be replaced with a GPI linker without impact on Wnt antagonism.	INTRO
+96	99	Wnt	protein_type	The transmembrane span and cytoplasmic tail can be replaced with a GPI linker without impact on Wnt antagonism.	INTRO
+4	14	structures	evidence	The structures presented here reveal the unknown fold of the WSC domain and the tight interactions of all three domains.	INTRO
+61	64	WSC	structure_element	The structures presented here reveal the unknown fold of the WSC domain and the tight interactions of all three domains.	INTRO
+58	85	LRP6PE3PE4-DKK1CRD2-KRM1ECD	complex_assembly	We further succeeded in determination of a low-resolution LRP6PE3PE4-DKK1CRD2-KRM1ECD complex, defining the architecture of the Wnt inhibitory complex that leads to Lrp6 cell-surface depletion.	INTRO
+128	131	Wnt	protein_type	We further succeeded in determination of a low-resolution LRP6PE3PE4-DKK1CRD2-KRM1ECD complex, defining the architecture of the Wnt inhibitory complex that leads to Lrp6 cell-surface depletion.	INTRO
+132	150	inhibitory complex	complex_assembly	We further succeeded in determination of a low-resolution LRP6PE3PE4-DKK1CRD2-KRM1ECD complex, defining the architecture of the Wnt inhibitory complex that leads to Lrp6 cell-surface depletion.	INTRO
+165	169	Lrp6	protein	We further succeeded in determination of a low-resolution LRP6PE3PE4-DKK1CRD2-KRM1ECD complex, defining the architecture of the Wnt inhibitory complex that leads to Lrp6 cell-surface depletion.	INTRO
+34	54	extracellular domain	structure_element	The recombinant production of the extracellular domain of Krm for structural studies proved challenging (see Experimental Procedures).	RESULTS
+58	61	Krm	protein_type	The recombinant production of the extracellular domain of Krm for structural studies proved challenging (see Experimental Procedures).	RESULTS
+66	84	structural studies	experimental_method	The recombinant production of the extracellular domain of Krm for structural studies proved challenging (see Experimental Procedures).	RESULTS
+26	30	KRM1	protein	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+30	33	ECD	structure_element	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+34	48	complexes with	protein_state	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+49	55	DKK1fl	protein	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+57	61	DKK1	protein	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+61	72	Linker-CRD2	structure_element	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+78	82	DKK1	protein	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+82	86	CRD2	structure_element	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+124	138	gel filtration	experimental_method	We succeeded in purifying KRM1ECD complexes with DKK1fl, DKK1Linker-CRD2, and DKK1CRD2 that were monodisperse and stable in gel filtration, hence indicating at least micromolar affinity (data not shown).	RESULTS
+8	21	crystal forms	evidence	Several crystal forms were obtained from these complexes, however, crystals always contained only KRM1 protein.	RESULTS
+67	75	crystals	evidence	Several crystal forms were obtained from these complexes, however, crystals always contained only KRM1 protein.	RESULTS
+98	102	KRM1	protein	Several crystal forms were obtained from these complexes, however, crystals always contained only KRM1 protein.	RESULTS
+3	9	solved	experimental_method	We solved the structure of KRM1ECD in three crystal forms at 1.9, 2.8, and 3.2 Å resolution (Table 1).	RESULTS
+14	23	structure	evidence	We solved the structure of KRM1ECD in three crystal forms at 1.9, 2.8, and 3.2 Å resolution (Table 1).	RESULTS
+27	31	KRM1	protein	We solved the structure of KRM1ECD in three crystal forms at 1.9, 2.8, and 3.2 Å resolution (Table 1).	RESULTS
+31	34	ECD	structure_element	We solved the structure of KRM1ECD in three crystal forms at 1.9, 2.8, and 3.2 Å resolution (Table 1).	RESULTS
+20	29	structure	evidence	The high-resolution structure is a near full-length model (Figure 1).	RESULTS
+40	51	full-length	protein_state	The high-resolution structure is a near full-length model (Figure 1).	RESULTS
+4	9	small	protein_state	The small, flexible, and charged 98AEHED102 loop could only be modeled in a slightly lower resolution structure and in crystal form III.	RESULTS
+11	19	flexible	protein_state	The small, flexible, and charged 98AEHED102 loop could only be modeled in a slightly lower resolution structure and in crystal form III.	RESULTS
+25	32	charged	protein_state	The small, flexible, and charged 98AEHED102 loop could only be modeled in a slightly lower resolution structure and in crystal form III.	RESULTS
+33	48	98AEHED102 loop	structure_element	The small, flexible, and charged 98AEHED102 loop could only be modeled in a slightly lower resolution structure and in crystal form III.	RESULTS
+102	111	structure	evidence	The small, flexible, and charged 98AEHED102 loop could only be modeled in a slightly lower resolution structure and in crystal form III.	RESULTS
+4	6	KR	structure_element	The KR, WSC, and CUB are arranged in a roughly triangular fashion with tight interactions between all three domains.	RESULTS
+8	11	WSC	structure_element	The KR, WSC, and CUB are arranged in a roughly triangular fashion with tight interactions between all three domains.	RESULTS
+17	20	CUB	structure_element	The KR, WSC, and CUB are arranged in a roughly triangular fashion with tight interactions between all three domains.	RESULTS
+4	6	KR	structure_element	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+43	62	glycosylation sites	site	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+93	110	disulfide bridges	ptm	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+112	115	C32	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+116	120	C114	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+122	125	C55	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+126	129	C95	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+131	134	C84	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+135	139	C109	residue_name_number	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+157	164	Kringle	structure_element	The KR domain, which bears two of the four glycosylation sites, contains the canonical three disulfide bridges (C32-C114, C55-C95, C84-C109) and, like other Kringle domains, is low in secondary structure elements.	RESULTS
+30	37	Kringle	structure_element	The structurally most similar Kringle domain is that of human plasminogen (PDB: 1PKR) with an root-mean-square deviation (RMSD) of 1.7 Å for 73 aligned Cα (Figure 1B).	RESULTS
+56	61	human	species	The structurally most similar Kringle domain is that of human plasminogen (PDB: 1PKR) with an root-mean-square deviation (RMSD) of 1.7 Å for 73 aligned Cα (Figure 1B).	RESULTS
+62	73	plasminogen	protein	The structurally most similar Kringle domain is that of human plasminogen (PDB: 1PKR) with an root-mean-square deviation (RMSD) of 1.7 Å for 73 aligned Cα (Figure 1B).	RESULTS
+94	120	root-mean-square deviation	evidence	The structurally most similar Kringle domain is that of human plasminogen (PDB: 1PKR) with an root-mean-square deviation (RMSD) of 1.7 Å for 73 aligned Cα (Figure 1B).	RESULTS
+122	126	RMSD	evidence	The structurally most similar Kringle domain is that of human plasminogen (PDB: 1PKR) with an root-mean-square deviation (RMSD) of 1.7 Å for 73 aligned Cα (Figure 1B).	RESULTS
+4	8	KRM1	protein	The KRM1 structure reveals the fold of the WSC domain for the first time.	RESULTS
+9	18	structure	evidence	The KRM1 structure reveals the fold of the WSC domain for the first time.	RESULTS
+43	46	WSC	structure_element	The KRM1 structure reveals the fold of the WSC domain for the first time.	RESULTS
+4	13	structure	evidence	The structure is best described as a sandwich of a β1-β5-β3-β4-β2 antiparallel β sheet and a single α helix.	RESULTS
+37	45	sandwich	structure_element	The structure is best described as a sandwich of a β1-β5-β3-β4-β2 antiparallel β sheet and a single α helix.	RESULTS
+51	86	β1-β5-β3-β4-β2 antiparallel β sheet	structure_element	The structure is best described as a sandwich of a β1-β5-β3-β4-β2 antiparallel β sheet and a single α helix.	RESULTS
+100	107	α helix	structure_element	The structure is best described as a sandwich of a β1-β5-β3-β4-β2 antiparallel β sheet and a single α helix.	RESULTS
+4	13	structure	evidence	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+30	35	loops	structure_element	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+62	79	disulfide bridges	ptm	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+81	85	C122	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+86	90	C186	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+92	96	C147	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+97	101	C167	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+103	107	C151	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+108	112	C169	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+114	118	C190	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+119	123	C198	residue_name_number	The structure is also rich in loops and is stabilized by four disulfide bridges (C122-C186, C147-C167, C151-C169, C190-C198).	RESULTS
+10	25	PDBeFold server	experimental_method	Using the PDBeFold server, we detected a surprising yet significant homology to PAN module domains.	RESULTS
+80	98	PAN module domains	structure_element	Using the PDBeFold server, we detected a surprising yet significant homology to PAN module domains.	RESULTS
+35	59	hepatocyte growth factor	protein_type	The closest structural relative is hepatocyte growth factor (HGF, PDB: 1GP9), which superposes with an RMSD of 2.3 Å for 58 aligned Cα (Figure 1B).	RESULTS
+61	64	HGF	protein_type	The closest structural relative is hepatocyte growth factor (HGF, PDB: 1GP9), which superposes with an RMSD of 2.3 Å for 58 aligned Cα (Figure 1B).	RESULTS
+84	94	superposes	experimental_method	The closest structural relative is hepatocyte growth factor (HGF, PDB: 1GP9), which superposes with an RMSD of 2.3 Å for 58 aligned Cα (Figure 1B).	RESULTS
+103	107	RMSD	evidence	The closest structural relative is hepatocyte growth factor (HGF, PDB: 1GP9), which superposes with an RMSD of 2.3 Å for 58 aligned Cα (Figure 1B).	RESULTS
+4	7	CUB	structure_element	The CUB domain bears two glycosylation sites.	RESULTS
+25	44	glycosylation sites	site	The CUB domain bears two glycosylation sites.	RESULTS
+37	53	electron density	evidence	Although present, the quality of the electron density around N217 did not allow modeling of the sugar moiety.	RESULTS
+61	65	N217	residue_name_number	Although present, the quality of the electron density around N217 did not allow modeling of the sugar moiety.	RESULTS
+3	17	crystal form I	evidence	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+21	28	calcium	chemical	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+70	84	coordinated by	bond_interaction	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+105	109	D263	residue_name_number	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+111	115	D266	residue_name_number	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+133	137	D306	residue_name_number	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+166	170	N309	residue_name_number	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+177	182	water	chemical	In crystal form I, a calcium ion is present at the canonical position coordinated by the carboxylates of D263, D266 (bidentate), and D306, as well as the carbonyl of N309 and a water molecule.	RESULTS
+4	23	coordination sphere	site	The coordination sphere deviates significantly from perfectly octahedral (not shown).	RESULTS
+72	79	calcium	chemical	This might result in the site having a low affinity and may explain why calcium is not present in the two low-resolution crystal forms.	RESULTS
+121	134	crystal forms	evidence	This might result in the site having a low affinity and may explain why calcium is not present in the two low-resolution crystal forms.	RESULTS
+0	7	Loss of	protein_state	Loss of calcium has led to loop rearrangements and partial disorder in these crystal forms.	RESULTS
+8	15	calcium	chemical	Loss of calcium has led to loop rearrangements and partial disorder in these crystal forms.	RESULTS
+27	31	loop	structure_element	Loss of calcium has led to loop rearrangements and partial disorder in these crystal forms.	RESULTS
+77	90	crystal forms	evidence	Loss of calcium has led to loop rearrangements and partial disorder in these crystal forms.	RESULTS
+39	44	CUB_C	structure_element	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+55	60	Tsg-6	protein	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+80	90	superposes	experimental_method	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+96	99	KRM	protein	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+99	102	CUB	structure_element	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+111	115	RMSD	evidence	The closest structural relative is the CUB_C domain of Tsg-6 (PDB: 2WNO), which superposes with KRMCUB with an RMSD of 1.6 Å for 104 Cα (Figure 1B).	RESULTS
+2	15	superposition	experimental_method	A superposition of the three KRM1 structures reveals no major structural differences (Figure 1C) as anticipated from the plethora of interactions between the three domains.	RESULTS
+29	33	KRM1	protein	A superposition of the three KRM1 structures reveals no major structural differences (Figure 1C) as anticipated from the plethora of interactions between the three domains.	RESULTS
+34	44	structures	evidence	A superposition of the three KRM1 structures reveals no major structural differences (Figure 1C) as anticipated from the plethora of interactions between the three domains.	RESULTS
+52	69	Ca2+ binding site	site	Minor differences are caused by the collapse of the Ca2+ binding site in crystal forms II and III and loop flexibility in the KR domain.	RESULTS
+73	97	crystal forms II and III	evidence	Minor differences are caused by the collapse of the Ca2+ binding site in crystal forms II and III and loop flexibility in the KR domain.	RESULTS
+102	106	loop	structure_element	Minor differences are caused by the collapse of the Ca2+ binding site in crystal forms II and III and loop flexibility in the KR domain.	RESULTS
+126	128	KR	structure_element	Minor differences are caused by the collapse of the Ca2+ binding site in crystal forms II and III and loop flexibility in the KR domain.	RESULTS
+4	9	F207S	mutant	The F207S mutation recently found to cause ectodermal dysplasia in Palestinian families maps to the hydrophobic core of the protein at the interface of the three subdomains (Figure 1A).	RESULTS
+100	116	hydrophobic core	site	The F207S mutation recently found to cause ectodermal dysplasia in Palestinian families maps to the hydrophobic core of the protein at the interface of the three subdomains (Figure 1A).	RESULTS
+139	148	interface	site	The F207S mutation recently found to cause ectodermal dysplasia in Palestinian families maps to the hydrophobic core of the protein at the interface of the three subdomains (Figure 1A).	RESULTS
+19	27	bound to	protein_state	Such a mutation is bound to severely destabilize the protein structure of KRM1, leading to disturbance of its Wnt antagonistic, Wnt stimulatory, and Wnt independent activity.	RESULTS
+74	78	KRM1	protein	Such a mutation is bound to severely destabilize the protein structure of KRM1, leading to disturbance of its Wnt antagonistic, Wnt stimulatory, and Wnt independent activity.	RESULTS
+110	113	Wnt	protein_type	Such a mutation is bound to severely destabilize the protein structure of KRM1, leading to disturbance of its Wnt antagonistic, Wnt stimulatory, and Wnt independent activity.	RESULTS
+128	131	Wnt	protein_type	Such a mutation is bound to severely destabilize the protein structure of KRM1, leading to disturbance of its Wnt antagonistic, Wnt stimulatory, and Wnt independent activity.	RESULTS
+149	152	Wnt	protein_type	Such a mutation is bound to severely destabilize the protein structure of KRM1, leading to disturbance of its Wnt antagonistic, Wnt stimulatory, and Wnt independent activity.	RESULTS
+0	18	Co-crystallization	experimental_method	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+22	26	LRP6	protein	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+26	32	PE3PE4	structure_element	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+38	42	DKK1	protein	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+42	46	CRD2	structure_element	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+52	56	LRP6	protein	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+56	59	PE1	structure_element	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+90	94	DKK1	protein	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+148	151	Wnt	protein_type	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+166	169	Dkk	protein_type	Co-crystallization of LRP6PE3PE4 with DKK1CRD2, and LRP6PE1 with an N-terminal peptide of DKK1 has provided valuable structural insight into direct Wnt inhibition by Dkk ligands.	RESULTS
+23	27	flat	protein_state	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+28	32	DKK1	protein	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+32	36	CRD2	structure_element	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+46	54	binds to	protein_state	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+59	76	third β propeller	structure_element	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+80	84	LRP6	protein	One face of the rather flat DKK1CRD2 fragment binds to the third β propeller of LRP6.	RESULTS
+0	19	Mutational analyses	experimental_method	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+45	49	LRP6	protein	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+49	52	PE3	structure_element	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+69	73	DKK1	protein	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+73	77	CRD2	structure_element	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+88	104	Krm binding site	site	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+127	130	Dkk	protein_type	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+148	157	receptors	protein_type	Mutational analyses further implied that the LRP6PE3-averted face of DKK1CRD2 bears the Krm binding site, hence suggesting how Dkk can recruit both receptors into a ternary complex.	RESULTS
+59	65	Lrp5/6	protein_type	To obtain direct insight into ternary complex formation by Lrp5/6, Dkk, and Krm, we subjected an LRP6PE3PE4-DKK1fl-KRM1ECD complex to crystallization trials.	RESULTS
+67	70	Dkk	protein_type	To obtain direct insight into ternary complex formation by Lrp5/6, Dkk, and Krm, we subjected an LRP6PE3PE4-DKK1fl-KRM1ECD complex to crystallization trials.	RESULTS
+76	79	Krm	protein_type	To obtain direct insight into ternary complex formation by Lrp5/6, Dkk, and Krm, we subjected an LRP6PE3PE4-DKK1fl-KRM1ECD complex to crystallization trials.	RESULTS
+97	122	LRP6PE3PE4-DKK1fl-KRM1ECD	complex_assembly	To obtain direct insight into ternary complex formation by Lrp5/6, Dkk, and Krm, we subjected an LRP6PE3PE4-DKK1fl-KRM1ECD complex to crystallization trials.	RESULTS
+134	156	crystallization trials	experimental_method	To obtain direct insight into ternary complex formation by Lrp5/6, Dkk, and Krm, we subjected an LRP6PE3PE4-DKK1fl-KRM1ECD complex to crystallization trials.	RESULTS
+0	16	Diffraction data	evidence	Diffraction data collected from the resulting crystals were highly anisotropic with diffraction extending in the best directions to 3.5 Å and 3.7 Å but only to 6.4 Å in the third direction.	RESULTS
+46	54	crystals	evidence	Diffraction data collected from the resulting crystals were highly anisotropic with diffraction extending in the best directions to 3.5 Å and 3.7 Å but only to 6.4 Å in the third direction.	RESULTS
+36	47	diffraction	evidence	Despite the lack of high-resolution diffraction, the general architecture of the ternary complex is revealed (Figure 2A).	RESULTS
+0	4	DKK1	protein	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+4	8	CRD2	structure_element	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+9	17	binds to	protein_state	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+38	42	LRP6	protein	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+43	46	PE3	structure_element	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+47	58	β propeller	structure_element	DKK1CRD2 binds to the top face of the LRP6 PE3 β propeller as described earlier for the binary complex.	RESULTS
+0	4	KRM1	protein	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+4	7	ECD	structure_element	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+20	27	bind on	protein_state	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+49	53	DKK1	protein	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+53	57	CRD2	structure_element	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+72	74	KR	structure_element	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+79	82	WSC	structure_element	KRM1ECD does indeed bind on the opposite side of DKK1CRD2 with only its KR and WSC domains engaged in binding (Figure 2A).	RESULTS
+45	60	crystallization	experimental_method	Although present in the complex subjected to crystallization, we observe no density that could correspond to CRD1 or the domain linker (L).	RESULTS
+76	83	density	evidence	Although present in the complex subjected to crystallization, we observe no density that could correspond to CRD1 or the domain linker (L).	RESULTS
+109	113	CRD1	structure_element	Although present in the complex subjected to crystallization, we observe no density that could correspond to CRD1 or the domain linker (L).	RESULTS
+121	134	domain linker	structure_element	Although present in the complex subjected to crystallization, we observe no density that could correspond to CRD1 or the domain linker (L).	RESULTS
+136	137	L	structure_element	Although present in the complex subjected to crystallization, we observe no density that could correspond to CRD1 or the domain linker (L).	RESULTS
+20	24	CRD2	structure_element	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+28	32	DKK1	protein	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+75	79	KRM1	protein	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+84	109	surface plasmon resonance	experimental_method	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+111	114	SPR	experimental_method	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+144	152	affinity	evidence	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+161	172	full-length	protein_state	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+173	177	DKK1	protein	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+194	198	KRM1	protein	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+198	201	ECD	structure_element	We confirm that the CRD2 of DKK1 is required and sufficient for binding to KRM1: In surface plasmon resonance (SPR), we measured low micromolar affinity between full-length DKK1 and immobilized KRM1ECD (Figure 2B).	RESULTS
+2	13	SUMO fusion	experimental_method	A SUMO fusion of DKK1L-CRD2 displayed a similar (slightly higher) affinity.	RESULTS
+17	27	DKK1L-CRD2	structure_element	A SUMO fusion of DKK1L-CRD2 displayed a similar (slightly higher) affinity.	RESULTS
+66	74	affinity	evidence	A SUMO fusion of DKK1L-CRD2 displayed a similar (slightly higher) affinity.	RESULTS
+15	26	SUMO fusion	experimental_method	In contrast, a SUMO fusion of DKK1CRD1-L did not display binding for concentrations tested up to 325 μM (Figure 2B).	RESULTS
+30	40	DKK1CRD1-L	structure_element	In contrast, a SUMO fusion of DKK1CRD1-L did not display binding for concentrations tested up to 325 μM (Figure 2B).	RESULTS
+13	32	DKK1-KRM1 interface	site	Overall, the DKK1-KRM1 interface is characterized by a large number of polar interactions but only few hydrophobic contacts (Figure 2C).	RESULTS
+71	89	polar interactions	bond_interaction	Overall, the DKK1-KRM1 interface is characterized by a large number of polar interactions but only few hydrophobic contacts (Figure 2C).	RESULTS
+103	123	hydrophobic contacts	bond_interaction	Overall, the DKK1-KRM1 interface is characterized by a large number of polar interactions but only few hydrophobic contacts (Figure 2C).	RESULTS
+4	21	crystal structure	evidence	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+47	51	DKK1	protein	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+101	105	R191	residue_name_number	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+109	113	DKK1	protein	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+129	140	salt bridge	bond_interaction	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+144	148	D125	residue_name_number	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+153	157	E162	residue_name_number	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+161	165	KRM1	protein	The crystal structure gives an explanation for DKK1 loss-of-binding mutations identified previously: R191 of DKK1 forms a double salt bridge to D125 and E162 of KRM1 (Figure 2C).	RESULTS
+2	17	charge reversal	experimental_method	A charge reversal as in the mouse Dkk1 (mDkk1) R197E variant would severely disrupt the binding.	RESULTS
+28	33	mouse	taxonomy_domain	A charge reversal as in the mouse Dkk1 (mDkk1) R197E variant would severely disrupt the binding.	RESULTS
+34	38	Dkk1	protein	A charge reversal as in the mouse Dkk1 (mDkk1) R197E variant would severely disrupt the binding.	RESULTS
+40	45	mDkk1	protein	A charge reversal as in the mouse Dkk1 (mDkk1) R197E variant would severely disrupt the binding.	RESULTS
+47	52	R197E	mutant	A charge reversal as in the mouse Dkk1 (mDkk1) R197E variant would severely disrupt the binding.	RESULTS
+15	19	K226	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+34	38	DKK1	protein	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+64	82	hydrophobic pocket	site	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+101	105	KRM1	protein	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+116	120	Y108	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+122	125	W94	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+131	135	W106	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+143	155	salt bridges	bond_interaction	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+180	184	KRM1	protein	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+185	188	D88	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+193	196	D90	residue_name_number	Similarly, the K226 side chain of DKK1, which points to a small hydrophobic pocket on the surface of KRM1 formed by Y108, W94, and W106, forms salt bridges with the side chains of KRM1 D88 and D90.	RESULTS
+9	24	charge reversal	experimental_method	Again, a charge reversal as shown before for mDkk1 K232E would be incompatible with binding.	RESULTS
+45	50	mDkk1	protein	Again, a charge reversal as shown before for mDkk1 K232E would be incompatible with binding.	RESULTS
+51	56	K232E	mutant	Again, a charge reversal as shown before for mDkk1 K232E would be incompatible with binding.	RESULTS
+18	22	DKK1	protein	The side chain of DKK1 S192 was also predicted to be involved in Krm binding.	RESULTS
+23	27	S192	residue_name_number	The side chain of DKK1 S192 was also predicted to be involved in Krm binding.	RESULTS
+65	68	Krm	protein_type	The side chain of DKK1 S192 was also predicted to be involved in Krm binding.	RESULTS
+52	56	D201	residue_name_number	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+60	64	KRM1	protein	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+75	89	hydrogen bonds	bond_interaction	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+143	147	S192	residue_name_number	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+149	154	mouse	taxonomy_domain	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+156	160	S198	residue_name_number	Indeed, we found (Figure 2C) that the side chain of D201 of KRM1 forms two hydrogen bonds to the side-chain hydroxyl and the backbone amide of S192 (mouse, S198).	RESULTS
+11	29	polar interactions	bond_interaction	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+53	57	N140	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+59	63	S163	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+69	73	Y165	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+89	93	KRM1	protein	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+98	102	DKK1	protein	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+125	129	W206	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+131	135	L190	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+141	145	C189	residue_name_number	Additional polar interactions are formed between the N140, S163, and Y165 side chains of KRM1 and DKK1 backbone carbonyls of W206, L190, and C189, respectively.	RESULTS
+16	20	DKK1	protein	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+21	25	R224	residue_name_number	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+29	44	hydrogen bonded	bond_interaction	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+48	52	Y105	residue_name_number	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+57	61	W106	residue_name_number	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+65	69	KRM1	protein	The carbonyl of DKK1 R224 is hydrogen bonded to Y105 and W106 of KRM1.	RESULTS
+20	23	Dkk	protein_type	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+24	49	charge reversal mutations	experimental_method	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+67	73	murine	taxonomy_domain	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+107	110	Krm	protein_type	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+119	124	K211E	mutant	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+129	134	R203E	mutant	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+136	141	mouse	taxonomy_domain	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+142	147	K217E	mutant	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+152	157	R209E	mutant	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+204	207	Dkk	protein_type	We suspect that the Dkk charge reversal mutations performed in the murine background and shown to diminish Krm binding K211E and R203E (mouse K217E and R209E) do so likely indirectly by disruption of the Dkk fold.	RESULTS
+25	42	DKK1 binding site	site	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+46	50	KRM1	protein	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+54	65	introducing	experimental_method	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+66	85	glycosylation sites	site	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+93	95	KR	structure_element	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+97	108	90DVS92→NVS	mutant	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+114	117	WSC	structure_element	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+119	132	189VCF191→NCS	mutant	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+158	161	DKK	protein	We further validated the DKK1 binding site on KRM1 by introducing glycosylation sites at the KR (90DVS92→NVS) and WSC (189VCF191→NCS) domains pointing toward DKK (Figures 2A and 2D).	RESULTS
+16	32	N-linked glycans	ptm	Introduction of N-linked glycans in protein-protein-binding sites is an established way of disrupting protein-binding interfaces.	RESULTS
+36	65	protein-protein-binding sites	site	Introduction of N-linked glycans in protein-protein-binding sites is an established way of disrupting protein-binding interfaces.	RESULTS
+102	128	protein-binding interfaces	site	Introduction of N-linked glycans in protein-protein-binding sites is an established way of disrupting protein-binding interfaces.	RESULTS
+5	15	ectodomain	structure_element	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+16	23	mutants	protein_state	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+58	67	wild-type	protein_state	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+145	148	SPR	experimental_method	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+155	166	full-length	protein_state	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+167	171	DKK1	protein	Both ectodomain mutants were secreted comparably with the wild-type, indicating correct folding, but failed to achieve any detectable binding in SPR using full-length DKK1 as analyte.	RESULTS
+15	21	mutant	protein_state	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+45	53	N-glycan	ptm	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+66	75	interface	site	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+83	86	CUB	structure_element	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+95	108	309NQA311→NQS	mutant	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+115	124	wild-type	protein_state	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+133	137	DKK1	protein	In contrast, a mutant carrying an additional N-glycan outside the interface at the CUB domain (309NQA311→NQS), was wild-type-like in DKK1 binding (Figure 2D).	RESULTS
+27	49	LRP6-KRM1 Binding Site	site	Identification of a Direct LRP6-KRM1 Binding Site	RESULTS
+4	31	LRP6PE3PE4-DKK1CRD2-KRM1ECD	complex_assembly	The LRP6PE3PE4-DKK1CRD2-KRM1ECD complex structure reveals no direct interactions between KRM1 and LRP6.	RESULTS
+40	49	structure	evidence	The LRP6PE3PE4-DKK1CRD2-KRM1ECD complex structure reveals no direct interactions between KRM1 and LRP6.	RESULTS
+89	93	KRM1	protein	The LRP6PE3PE4-DKK1CRD2-KRM1ECD complex structure reveals no direct interactions between KRM1 and LRP6.	RESULTS
+98	102	LRP6	protein	The LRP6PE3PE4-DKK1CRD2-KRM1ECD complex structure reveals no direct interactions between KRM1 and LRP6.	RESULTS
+35	47	complex with	protein_state	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+59	70	full-length	protein_state	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+71	75	LRP6	protein	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+76	86	ectodomain	structure_element	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+88	100	PE1PE2PE3PE4	structure_element	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+101	111	horse shoe	structure_element	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+155	174	electron microscopy	experimental_method	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+176	178	EM	experimental_method	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+183	211	small-angle X-ray scattering	experimental_method	We constructed in silico a ternary complex with a close to full-length LRP6 ectodomain (PE1PE2PE3PE4 horse shoe) similar to but without refinement against electron microscopy (EM) or small-angle X-ray scattering data.	RESULTS
+13	19	PE3PE4	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+33	45	superimposed	experimental_method	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+50	53	PE4	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+59	62	PE3	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+70	87	crystal structure	evidence	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+97	101	LRP6	protein	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+101	107	PE1PE2	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+108	117	structure	evidence	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+122	134	superimposed	experimental_method	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+139	142	PE2	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+148	151	PE3	structure_element	An auxiliary PE3PE4 fragment was superimposed via PE4 onto PE3 of the crystal structure, and the LRP6PE1PE2 structure was superimposed via PE2 onto PE3 of this auxiliary fragment (Figure 3A).	RESULTS
+98	117	Ca2+-binding region	site	For this crude approximation of a true ternary complex, we noted very close proximity between the Ca2+-binding region of KRM1 and the top face of the PE2 β propeller of LRP6.	RESULTS
+121	125	KRM1	protein	For this crude approximation of a true ternary complex, we noted very close proximity between the Ca2+-binding region of KRM1 and the top face of the PE2 β propeller of LRP6.	RESULTS
+150	153	PE2	structure_element	For this crude approximation of a true ternary complex, we noted very close proximity between the Ca2+-binding region of KRM1 and the top face of the PE2 β propeller of LRP6.	RESULTS
+154	165	β propeller	structure_element	For this crude approximation of a true ternary complex, we noted very close proximity between the Ca2+-binding region of KRM1 and the top face of the PE2 β propeller of LRP6.	RESULTS
+169	173	LRP6	protein	For this crude approximation of a true ternary complex, we noted very close proximity between the Ca2+-binding region of KRM1 and the top face of the PE2 β propeller of LRP6.	RESULTS
+4	19	solvent-exposed	protein_state	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+29	33	R307	residue_name_number	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+35	39	I308	residue_name_number	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+45	49	N309	residue_name_number	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+65	95	Ca2+-binding β connection loop	structure_element	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+99	103	KRM1	protein	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+193	205	binding site	site	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+209	221	β propellers	structure_element	The solvent-exposed residues R307, I308, and N309 of the central Ca2+-binding β connection loop of KRM1 would be almost ideally positioned for binding to this face, which is commonly used as a binding site on β propellers.	RESULTS
+20	28	arginine	residue_name	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+29	35	lysine	residue_name	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+37	47	isoleucine	residue_name	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+53	63	asparagine	residue_name	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+84	97	N-X-I-(G)-R/K	structure_element	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+120	124	DKK1	protein	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+129	133	SOST	protein	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+145	149	LRP6	protein	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+161	172	propeller 1	structure_element	Peptides containing arginine/lysine, isoleucine, and asparagine (consensus sequence N-X-I-(G)-R/K) are also employed by DKK1 and SOST to bind to LRP6 (albeit to propeller 1; Figure 3B).	RESULTS
+31	35	KRM1	protein	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+35	38	CUB	structure_element	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+39	47	binds to	protein_state	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+48	52	LRP6	protein	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+52	55	PE2	structure_element	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+65	68	SPR	experimental_method	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+97	106	wild-type	protein_state	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+115	130	GlycoCUB mutant	protein_state	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+134	138	KRM1	protein	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+138	141	ECD	structure_element	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+154	174	N-glycosylation site	site	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+178	182	N309	residue_name_number	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+200	204	LRP6	protein	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+204	210	PE1PE2	structure_element	To support the hypothesis that KRM1CUB binds to LRP6PE2, we used SPR and compared binding of the wild-type and the GlycoCUB mutant of KRM1ECD (bearing an N-glycosylation site at N309) with a purified LRP6PE1PE2 fragment.	RESULTS
+29	39	absence of	protein_state	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+40	43	Dkk	protein_type	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+45	49	KRM1	protein	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+49	52	ECD	structure_element	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+53	58	bound	protein_state	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+86	88	to	protein_state	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+89	93	LRP6	protein	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+93	99	PE1PE2	structure_element	Indeed, we found that in the absence of Dkk, KRM1ECD bound with considerable affinity to LRP6PE1PE2 (Figure 3C).	RESULTS
+55	59	KRM1	protein	In contrast, no saturable binding was observed between KRM1 and LRP6PE3PE4.	RESULTS
+64	68	LRP6	protein	In contrast, no saturable binding was observed between KRM1 and LRP6PE3PE4.	RESULTS
+68	74	PE3PE4	structure_element	In contrast, no saturable binding was observed between KRM1 and LRP6PE3PE4.	RESULTS
+0	15	Introduction of	experimental_method	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+19	39	N-glycosylation site	site	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+43	47	N309	residue_name_number	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+51	55	KRM1	protein	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+55	58	ECD	structure_element	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+69	73	LRP6	protein	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+73	79	PE1PE2	structure_element	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+118	122	DKK1	protein	Introduction of an N-glycosylation site at N309 in KRM1ECD abolished LRP6PE1PE2 binding (Figure 3C), while binding to DKK1 was unaffected (Figure 2D).	RESULTS
+31	43	binding site	site	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+52	56	KRM1	protein	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+56	59	CUB	structure_element	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+64	68	LRP6	protein	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+68	71	PE2	structure_element	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+119	127	Lrp6-Krm	complex_assembly	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+170	173	Wnt	protein_type	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+204	208	Lrp6	protein	We conclude that the predicted binding site between KRM1CUB and LRP6PE2 is a strong candidate for mediating the direct Lrp6-Krm interaction, which is thought to increase Wnt responsiveness by stabilizing Lrp6 at the cell surface.	RESULTS
+55	67	binding site	site	Further experiments are required to pinpoint the exact binding site.	RESULTS
+9	13	LRP6	protein	Although LRP6PE1 appears somewhat out of reach in the modeled ternary complex, it cannot be excluded as the Krm binding site in the ternary complex and LRP6-Krm binary complex.	RESULTS
+13	16	PE1	structure_element	Although LRP6PE1 appears somewhat out of reach in the modeled ternary complex, it cannot be excluded as the Krm binding site in the ternary complex and LRP6-Krm binary complex.	RESULTS
+108	124	Krm binding site	site	Although LRP6PE1 appears somewhat out of reach in the modeled ternary complex, it cannot be excluded as the Krm binding site in the ternary complex and LRP6-Krm binary complex.	RESULTS
+152	160	LRP6-Krm	complex_assembly	Although LRP6PE1 appears somewhat out of reach in the modeled ternary complex, it cannot be excluded as the Krm binding site in the ternary complex and LRP6-Krm binary complex.	RESULTS
+4	15	presence of	protein_state	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+16	19	DKK	protein	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+37	46	propeller	structure_element	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+48	51	PE1	structure_element	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+59	62	PE2	structure_element	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+67	71	LRP6	protein	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+89	92	Krm	protein_type	The presence of DKK may govern which propeller (PE1 versus PE2) of LRP6 is available for Krm binding.	RESULTS
+37	62	KRM1CUB-LRP6PE2 interface	site	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+93	96	Krm	protein_type	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+121	125	LRP6	protein	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+125	128	PE3	structure_element	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+133	137	DKK1	protein	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+137	141	CRD2	structure_element	Apparent binding across the proposed KRM1CUB-LRP6PE2 interface is expected to be higher once Krm is also cross-linked to LRP6PE3 via DKK1CRD2 (Figure 3D).	RESULTS
+15	32	negative-stain EM	experimental_method	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+37	65	small-angle X-ray scattering	experimental_method	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+77	81	LRP6	protein	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+81	93	PE1PE2PE3PE4	structure_element	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+95	107	in isolation	protein_state	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+112	127	in complex with	protein_state	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+128	132	Dkk1	protein_type	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+139	156	negative-stain EM	experimental_method	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+160	171	full-length	protein_state	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+172	176	LRP6	protein	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+177	187	ectodomain	structure_element	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+204	210	curved	protein_state	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+212	225	platform-like	protein_state	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+279	282	PE2	structure_element	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+287	290	PE3	structure_element	Low-resolution negative-stain EM and small-angle X-ray scattering studies of LRP6PE1PE2PE3PE4, in isolation and in complex with Dkk1, plus negative-stain EM of full-length LRP6 ectodomain, have indicated curved, platform-like conformations but also potential flexibility between PE2 and PE3.	RESULTS
+47	50	Krm	protein_type	It is therefore possible that the interplay of Krm and Dkk binding can promote changes in LRP6 ectodomain conformation with functional consequences; however, such ideas await investigation.	RESULTS
+55	58	Dkk	protein_type	It is therefore possible that the interplay of Krm and Dkk binding can promote changes in LRP6 ectodomain conformation with functional consequences; however, such ideas await investigation.	RESULTS
+90	94	LRP6	protein	It is therefore possible that the interplay of Krm and Dkk binding can promote changes in LRP6 ectodomain conformation with functional consequences; however, such ideas await investigation.	RESULTS
+95	105	ectodomain	structure_element	It is therefore possible that the interplay of Krm and Dkk binding can promote changes in LRP6 ectodomain conformation with functional consequences; however, such ideas await investigation.	RESULTS
+20	54	structural and biophysical studies	experimental_method	Taken together, the structural and biophysical studies we report here extend our mechanistic understanding of Wnt signal regulation.	RESULTS
+110	113	Wnt	protein_type	Taken together, the structural and biophysical studies we report here extend our mechanistic understanding of Wnt signal regulation.	RESULTS
+16	26	ectodomain	structure_element	We describe the ectodomain structure of the dual Wnt regulator Krm1, providing an explanation for the detrimental effect on health and development of a homozygous KRM1 mutation.	RESULTS
+27	36	structure	evidence	We describe the ectodomain structure of the dual Wnt regulator Krm1, providing an explanation for the detrimental effect on health and development of a homozygous KRM1 mutation.	RESULTS
+49	52	Wnt	protein_type	We describe the ectodomain structure of the dual Wnt regulator Krm1, providing an explanation for the detrimental effect on health and development of a homozygous KRM1 mutation.	RESULTS
+63	67	Krm1	protein_type	We describe the ectodomain structure of the dual Wnt regulator Krm1, providing an explanation for the detrimental effect on health and development of a homozygous KRM1 mutation.	RESULTS
+163	167	KRM1	protein	We describe the ectodomain structure of the dual Wnt regulator Krm1, providing an explanation for the detrimental effect on health and development of a homozygous KRM1 mutation.	RESULTS
+39	46	Krm-Dkk	complex_assembly	We also reveal the interaction mode of Krm-Dkk and the architecture of the ternary complex formed by Lrp5/6, Dkk, and Krm.	RESULTS
+101	107	Lrp5/6	protein_type	We also reveal the interaction mode of Krm-Dkk and the architecture of the ternary complex formed by Lrp5/6, Dkk, and Krm.	RESULTS
+109	112	Dkk	protein_type	We also reveal the interaction mode of Krm-Dkk and the architecture of the ternary complex formed by Lrp5/6, Dkk, and Krm.	RESULTS
+118	121	Krm	protein_type	We also reveal the interaction mode of Krm-Dkk and the architecture of the ternary complex formed by Lrp5/6, Dkk, and Krm.	RESULTS
+25	42	crystal structure	evidence	Furthermore, the ternary crystal structure has guided in silico and biophysical analyses to suggest a direct LRP6-KRM1 interaction site.	RESULTS
+54	88	in silico and biophysical analyses	experimental_method	Furthermore, the ternary crystal structure has guided in silico and biophysical analyses to suggest a direct LRP6-KRM1 interaction site.	RESULTS
+109	135	LRP6-KRM1 interaction site	site	Furthermore, the ternary crystal structure has guided in silico and biophysical analyses to suggest a direct LRP6-KRM1 interaction site.	RESULTS
+136	139	Krm	protein_type	Our findings provide a solid foundation for additional studies to probe how ternary complex formation triggers internalization, whereas Krm binding in the absence of Dkk stabilizes the Wnt co-receptor at the cell surface.	RESULTS
+155	165	absence of	protein_state	Our findings provide a solid foundation for additional studies to probe how ternary complex formation triggers internalization, whereas Krm binding in the absence of Dkk stabilizes the Wnt co-receptor at the cell surface.	RESULTS
+166	169	Dkk	protein_type	Our findings provide a solid foundation for additional studies to probe how ternary complex formation triggers internalization, whereas Krm binding in the absence of Dkk stabilizes the Wnt co-receptor at the cell surface.	RESULTS
+185	188	Wnt	protein_type	Our findings provide a solid foundation for additional studies to probe how ternary complex formation triggers internalization, whereas Krm binding in the absence of Dkk stabilizes the Wnt co-receptor at the cell surface.	RESULTS
+189	200	co-receptor	protein_type	Our findings provide a solid foundation for additional studies to probe how ternary complex formation triggers internalization, whereas Krm binding in the absence of Dkk stabilizes the Wnt co-receptor at the cell surface.	RESULTS
+0	9	Structure	evidence	Structure of Unliganded KRM1ECD	FIG
+13	23	Unliganded	protein_state	Structure of Unliganded KRM1ECD	FIG
+24	28	KRM1	protein	Structure of Unliganded KRM1ECD	FIG
+28	31	ECD	structure_element	Structure of Unliganded KRM1ECD	FIG
+8	12	KRM1	protein	(A) The KRM1ECD fold (crystal form I) colored blue to red from the N to C terminus.	FIG
+12	15	ECD	structure_element	(A) The KRM1ECD fold (crystal form I) colored blue to red from the N to C terminus.	FIG
+22	36	crystal form I	evidence	(A) The KRM1ECD fold (crystal form I) colored blue to red from the N to C terminus.	FIG
+0	9	Cysteines	residue_name	Cysteines as ball and sticks, glycosylation sites as sticks.	FIG
+30	49	glycosylation sites	site	Cysteines as ball and sticks, glycosylation sites as sticks.	FIG
+10	17	calcium	chemical	The bound calcium is shown as a gray sphere.	FIG
+16	21	F207S	mutant	The site of the F207S mutation associated with ectodermal dysplasia in humans is shown as mesh.	FIG
+71	77	humans	species	The site of the F207S mutation associated with ectodermal dysplasia in humans is shown as mesh.	FIG
+4	17	Superposition	experimental_method	(B) Superposition of the three KRM1ECD subdomains (solid) with their next structurally characterized homologs (half transparent).	FIG
+31	35	KRM1	protein	(B) Superposition of the three KRM1ECD subdomains (solid) with their next structurally characterized homologs (half transparent).	FIG
+35	38	ECD	structure_element	(B) Superposition of the three KRM1ECD subdomains (solid) with their next structurally characterized homologs (half transparent).	FIG
+4	17	Superposition	experimental_method	(C) Superposition of KRM1ECD from the three crystal forms.	FIG
+21	25	KRM1	protein	(C) Superposition of KRM1ECD from the three crystal forms.	FIG
+25	28	ECD	structure_element	(C) Superposition of KRM1ECD from the three crystal forms.	FIG
+44	57	crystal forms	evidence	(C) Superposition of KRM1ECD from the three crystal forms.	FIG
+0	16	Alignment scores	evidence	Alignment scores for each pairing are indicated on the dashed triangle.	FIG
+8	17	structure	evidence	(A) The structure of the ternary LRP6PE3PE4-DKK1CRD2-KRM1ECD complex.	FIG
+33	60	LRP6PE3PE4-DKK1CRD2-KRM1ECD	complex_assembly	(A) The structure of the ternary LRP6PE3PE4-DKK1CRD2-KRM1ECD complex.	FIG
+0	4	DKK1	protein	DKK1 (orange) is sandwiched between the PE3 module of LRP6 (blue) and the KR-WSC domain pair of KRM1 (green).	FIG
+40	43	PE3	structure_element	DKK1 (orange) is sandwiched between the PE3 module of LRP6 (blue) and the KR-WSC domain pair of KRM1 (green).	FIG
+54	58	LRP6	protein	DKK1 (orange) is sandwiched between the PE3 module of LRP6 (blue) and the KR-WSC domain pair of KRM1 (green).	FIG
+74	80	KR-WSC	structure_element	DKK1 (orange) is sandwiched between the PE3 module of LRP6 (blue) and the KR-WSC domain pair of KRM1 (green).	FIG
+96	100	KRM1	protein	DKK1 (orange) is sandwiched between the PE3 module of LRP6 (blue) and the KR-WSC domain pair of KRM1 (green).	FIG
+36	61	N-glycan attachment sites	site	Colored symbols indicate introduced N-glycan attachment sites (see D).	FIG
+4	7	SPR	experimental_method	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+34	45	full-length	protein_state	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+46	50	DKK1	protein	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+55	67	SUMO fusions	experimental_method	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+71	75	DKK1	protein	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+115	124	wild-type	protein_state	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+125	129	KRM1	protein	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+129	132	ECD	structure_element	(B) SPR data comparing binding of full-length DKK1 and SUMO fusions of DKK1 truncations for binding to immobilized wild-type KRM1ECD.	FIG
+25	51	DKK1CRD2-KRM1ECD interface	site	(C) Close-up view of the DKK1CRD2-KRM1ECD interface.	FIG
+21	30	interface	site	Residues involved in interface formation are shown as sticks; those mentioned in the text are labeled.	FIG
+0	12	Salt bridges	bond_interaction	Salt bridges are in pink and hydrogen bonds in black.	FIG
+29	43	hydrogen bonds	bond_interaction	Salt bridges are in pink and hydrogen bonds in black.	FIG
+4	7	SPR	experimental_method	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+8	20	binding data	evidence	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+31	35	DKK1	protein	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+57	66	wild-type	protein_state	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+67	71	KRM1	protein	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+71	74	ECD	structure_element	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+102	112	engineered	protein_state	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+113	132	glycosylation sites	site	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+140	142	KR	structure_element	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+147	150	WSC	structure_element	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+187	191	DKK1	protein	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+204	207	CUB	structure_element	(D) SPR binding data comparing DKK1 analyte binding with wild-type KRM1ECD and three variants bearing engineered glycosylation sites on the KR and WSC domains (green and blue pointing to DKK1) and on the CUB domain (orange).	FIG
+0	9	LRP6-KRM1	complex_assembly	LRP6-KRM1 Direct Interaction and Summary	FIG
+35	47	complex with	protein_state	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+57	69	β propellers	structure_element	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+73	77	LRP6	protein	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+78	84	intact	protein_state	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+90	93	CUB	structure_element	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+116	135	Ca2+-binding region	site	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+163	181	second β propeller	structure_element	(A) In a construction of a ternary complex with all four β propellers of LRP6 intact, the CUB domain points via its Ca2+-binding region toward the top face of the second β propeller.	FIG
+35	51	interaction site	site	(B) Close-up view of the potential interaction site.	FIG
+13	17	LRP6	protein	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+17	20	PE2	structure_element	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+30	42	superimposed	experimental_method	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+48	52	DKK1	protein	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+66	70	SOST	protein	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+99	103	LRP6	protein	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+103	106	PE1	structure_element	In addition, LRP6PE2 has been superimposed with DKK1 (yellow) and SOST (pink) peptide complexes of LRP6PE1.	FIG
+4	20	SPR measurements	experimental_method	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+31	35	LRP6	protein	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+35	41	PE1PE2	structure_element	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+55	64	wild-type	protein_state	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+65	69	KRM1	protein	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+69	72	ECD	structure_element	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+81	96	GlycoCUB mutant	protein_state	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+108	116	N-glycan	ptm	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+120	124	N309	residue_name_number	(C) SPR measurements comparing LRP6PE1PE2 binding with wild-type KRM1ECD and the GlycoCUB mutant bearing an N-glycan at N309.	FIG
+95	98	Wnt	protein_type	(D) Schematic representation of structural and biophysical findings and their implications for Wnt-dependent (left, middle) and independent (right) signaling.	FIG
+48	52	LRP6	protein	Conformational differences in the depictions of LRP6 are included purely for ease of representation.	FIG
+0	37	Diffraction and Refinement Statistics	evidence	Diffraction and Refinement Statistics	TABLE
+1	5	KRM1	protein	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+5	8	ECD	structure_element	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+9	13	KRM1	protein	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+13	16	ECD	structure_element	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+17	21	KRM1	protein	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+21	24	ECD	structure_element	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+25	29	KRM1	protein	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+29	32	ECD	structure_element	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+33	59	LRP6PE3PE4-DKKCRD2-KRM1ECD	complex_assembly	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+1295	1300	Water	chemical	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+1417	1422	Water	chemical	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+1466	1470	RMSD	evidence	"	KRM1ECD	KRM1ECD	KRM1ECD	KRM1ECD	LRP6PE3PE4-DKKCRD2-KRM1ECD	 	Crystal form	I	I	II	III	I	 	X-ray source	Diamond i04	Diamond i03	Diamond i03	Diamond i04	Diamond i04	 	Wavelength (Å)	0.9793	0.9700	0.9700	0.9795	0.9795	 	Space group	P3121	P3121	P43	P41212	C2221	 	Unit cell a/α (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	86.9/90	 	b/β (Å/°)	50.9/90	50.5/90	65.8/90	67.8/90	100.1/90	 	c/γ (Å/°)	188.4/120	187.4/120	75.0/90	198.2/90	270.7/90	 	Wilson B factor (Å2)	31	41	76	77	NA	 	Resolution range (Å)	47.10–1.90 (1.95–1.90)	62.47–2.10 (2.16–2.10)	75.00–2.80 (2.99–2.80)	67.80–3.20 (3.42–3.20)	67.68–3.50 (7.16–6.40, 3.92–3.50)	 	Unique reflections	23,300 (1,524)	17,089 (1,428)	7,964 (1,448)	8,171 (1,343)	8,070 (723, 645)	 	Average multiplicity	9.1 (9.2)	5.2 (5.3)	3.7 (3.7)	22.7 (12.6)	3.8 (3.5, 4.4)	 	Completeness (%)	99.8 (98.5)	100 (100)	99.8 (100)	98.8 (93.4)	51.6 (98.5, 14.1)	 	<I/σI>	11.4 (1.7)	12.0 (1.7)	14.9 (1.5)	13.1 (1.9)	4.6 (4.1, 2.2)	 	Rmerge (%)	14.8 (158.3)	9.3 (98.0)	6.2 (98.9)	29.8 (142.2)	44.9 (40.5, 114.2)	 	Rpim (%)	15.7 (55.3)	10.3 (109.0)	3.7 (53.8)	6.3 (40.0)	24.7 (23.9, 59.9)	 		 	Refinement	 		 	Rwork (%)	17.9	18.4	21.6	20.2	32.1	 	Rfree (%)	22.7	23.2	30.7	27.1	35.5	 		 	No. of Non-Hydrogen Atoms	 		 	Protein	2,260	2,301	2,102	2,305	7,730	 	N-glycans	42	42	28	28	0	 	Water	79	54	0	2	0	 	Ligands	6	6	2	5	0	 		 	Average B factor (Å2)	 		 	Protein	63	65	108	84	–	 	N-glycans	35	46	102	18	–	 	Water	68	85	–	75	–	 	Ligands	36	47	91	75	66	 		 	RMSD from Ideality	 		 	Bond lengths (Å)	0.020	0.016	0.019	0.016	0.004	 	Bond angles (°)	2.050	1.748	1.952	1.796	0.770	 		 	Ramachandran Plot	 		 	Favored (%)	96.8	95.5	96.9	94.9	92.3	 	Allowed (%)	99.7	100.0	100.0	99.7	99.8	 	Number of outliers	1	0	0	1	2	 	PDB code	5FWS	5FWT	5FWU	5FWV	5FWW	 	"	TABLE
+99	115	diffraction data	evidence	An additional shell given for the ternary complex corresponds to the last shell with near-complete diffraction data.	TABLE