Protein: DP03316 (UniProt P06149)
Region: residues 320	to 376
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
During model building, it became clear that a '50 residue portion of the D-LDH structure is disordered. The disordered region exhibits electron density that is discontinuous and untraceable in both the original multiple-wavelength anomalous diffraction electron density map and the final refined maps. 
Overall Structure. The D-LDH structure is composed of three discontinuous domains: the FAD-binding domain (residues 1–268 and 520–571), the cap domain (residues 269–310, 388–425, and 450–519), and the membrane-binding domain (residues 311–387 and 426–449, of which residues 329–376 are in the disordered region) (Fig. 1).
We propose a model for the association of D-LDH to the membrane. We note that there are nine other positive residues (Lys-331, Lys-336, Lys-344, Arg-346, Lys-353, Lys-355, Arg-358, Arg-364, and Lys-368) in the membrane-binding domain but not modeled in the discontinuous density map. These are shown as yellow balls in Fig. 4. A possible explanation for this disordered segment may be the absence of detergent or lipid in the
crystallization solution. That is, this region may not have a defined structure until it binds the membrane, or it may have a defined structure but with several orientations with respect to the rest of the molecule. Therefore, we propose that positive residues, both from the observed structure and possibly from the missing segment, facilitate the interaction of D-LDH with the negatively charged phosphate groups of the phospholipid membrane.
Another mechanism proposed for association of peripheral membrane proteins with the membrane is through a mixture of hydrophobic and electrostatic interactions (4, 5). The membrane-binding domain of D-LDH contains 16 apolar residues, nine in the observed structure and seven in the disordered region. Notably, all of the nine residues in the observed structure are distributed on a surface close to the cap domain and away
from the membrane-binding surface.
Fig. 1. Ribbon representation of the D-LDH molecule complexed with FAD. The three domains are: in cyan, the FAD-binding domain; in purple, the cap
domain; and in blue, the membrane-binding domain. The 50 missing residues
from the membrane-binding domain lie between Met-328 and Ser-375.
A putative model of the 50 missing residues (329–374) (yellow segment in Fig. 4), was built to attach both ends to the structure (residues 328 to 329 and 374 to 375) (blue segment in Fig. 4). This model seems reasonable, given that the solvent content of the crystal is small (30%), which results in tight crystal packing of symmetry-related molecules, especially in the vicinity of the missing residues, constraining the model of this segment.
Fig. 4. Cartoon of D-LDH associating with the membrane. D-LDH is anchored to the membrane by electrostatic interactions between basic residues (blue balls) from the observed membrane-binding domain
(blue) and possibly from the modeled missing segment (dashed yellow) comprising nine basic residues (yellow balls) and the negatively charged phospholipid head groups (red balls) of the membrane. 
Cross-references: PDB:1F0X