Protein: Internalin B (P0DQD3)
Organism: Listeria monocytogenes serotype 1/2a (strain EGD / Mackaness)
Function: Mediates the entry of L.monocytogenes into normally non- phagocytic mammalian host cells (Probable). Its host receptor is hepatocyte growth factor receptor (HGF receptor, a tyrosine kinase, MET) which is tyrosine- phosphorylated in response to InlB in human, green monkey, mouse and dog cell lines. Downstream adapter proteins GAB1 and CBL are phosphorylated in response to InlB, which also causes cell colony scattering. InlB binding to mammalian cells is saturable and inhibited by EDTA; InlB-coated beads can be taken up by host cells. Complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) might act as an InlB receptor, leading to activation of PI3-kinase in green monkey cells . Stimulation of Tyr-phosphorylation by InlB is antagonized by C1QBP, showing that potentiation of MET signaling via the GW domains is not mediated by C1QBP; the exact role of C1QBP remains to be determined. Stimulation of Tyr- phosphorylation of MET by InlB is potentiated by the InlB GW domains and glycosaminoglycans such as heparin; exogenously added InlB, or hepatocyte growth factor (HGF) will also substitute for bacterial InlB, suggesting InlB promotes bacterial invasion by mimicking the hormone HGF. May stimulate phosphatidylinositol 4,5- bisphosphate 3-kinase (PI3-kinase) in green monkey cells, has less effect in humans as PI3-kinase is constitutively and highly expressed in Caco cells (Probable). Binds heparin; C1QBP and heparin seem to bind to the GW domains
Subcellular location: Secreted. Cell surface. Cell membrane. Note=Approximately half the protein is secreted. Cell surface association is mediated by the GW domains and can occur when protein is added externally; externally added protein confers invasion competence . Replacement of the GW region with that of the Ami protein, which has 8 GW domains, localizes all the protein to the cell surface. Replacement of the GW region with GW5 and 6 of the Ami protein restores cell invasion when bacteria plus protein are added externally. Protein is homogenously distributed but partially buried in the cell membrane; it binds non-covalently to lipoteichoic acid (LTA) on the bacterial membrane, and can be released from the surface by LTA
InterPro domains:
- IPR014755: Copper resistance protein CopC/internalin, immunoglobulin-like (homologous_superfamily) [243-321]
- IPR013378: Internalin B-like, B-repeat (repeat) [323-392]
- IPR003591: Leucine-rich repeat, typical subtype (repeat) [97-230]
- IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [34-242]
- IPR025875: Leucine rich repeat 4 (repeat) [142-227]
- IPR024634: Internalin, N-terminal (domain) [33-76]
- IPR050836: SDS22/Internalin LRR-containing (family) [33-237]
- IPR025987: GW domain (domain) [393-630]
- IPR014756: Immunoglobulin E-set (homologous_superfamily) [241-320]
- IPR042229: Listeria-Bacteroides repeat domain superfamily (homologous_superfamily) [322-391]
- IPR001611: Leucine-rich repeat (repeat) [99-230]
- IPR012569: Internalin, Ig-like inter-repeat region (domain) [264-320]
- IPR038200: GW domain superfamily (homologous_superfamily) [392-630]
Sequence:
MKEKHNPRRKYCLISGLAIIFSLWIIIGNGAKVQAETITVSTPIKQIFPDDAFAETIKDNLKKKSVTDAVTQNELNSIDQIIANNSDIKSVQGIQYLPNVTKLFLNGNKLTDIKPLTNLKNLGWLFLDENKIKDLSSLKDLKKLKSLSLEHNGISDINGLVHLPQLESLYLGNNKITDITVLSRLTKLDTLSLEDNQISDIVPLAGLTKLQNLYLSKNHISDLRALAGLKNLDVLELFSQECLNKPINHQSNLVVPNTVKNTDGSLVTPEIISDDGDYEKPNVKWHLPEFTNEVSFIFYQPVTIGKAKARFHGRVTQPLKEVYTVSYDVDGTVIKTKVEAGTRITAPKPPTKQGYVFKGWYTEKNGGHEWNFNTDYMSGNDFTLYAVFKAETTEKTVNLTRYVKYIRGNAGIYKLPREDNSLKQGTLASHRCKALTVDREARNGGKLWYRLKNIGWTKAENLSLDRYDKMEYDKGVTAYARVRNASGNSVWTKPYNTAGAKHVNKLSVYQGKNMRILREAKTPITTWYQFSIGGKVIGWVDTRALNTFYKQSMEKPTRLTRYVSANKAGESYYKVPVADNPVKRGTLAKYKNQKLIVDCQATIEGQLWYRIRTSSTFIGWTKAANLRAQK
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0044403 (biological process involved in symbiotic interaction), GO:0051701 (biological process involved in interaction with host), GO:0044000 (movement in host), GO:0044409 (entry into host)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0030312 (external encapsulating structure), GO:0005618 (cell wall), GO:0009274 (peptidoglycan-based cell wall)