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Details on Person UniProt:P0DQD2 inlB

Class:IdReferenceGeneProduct:9637755
_chainChangeLogsignal peptide:1-30 for 9637755 added on Thu May 2 2019;chain:31-630 for 9637755 added on Thu May 2 2019
_displayNameUniProt:P0DQD2 inlB
_timestamp2024-08-09 18:43:46
chainsignal peptide:1-30
chain:31-630
checksumCA05F31BEFE9748C
commentFUNCTION Mediates the entry of L.monocytogenes into normally non-phagocytic mammalian host cells (PubMed:19900460). Its host receptor is hepatocyte growth factor receptor (HGF receptor, a tyrosine kinase, MET) which is tyrosine-phosphorylated in response to InlB. Downstream targets MAPK1/MAPK3 (Erk1/2) and AKT are phosphorylated in response to InlB, which also causes cell colony scattering (PubMed:19900460, PubMed:21345802, PubMed:22887347, PubMed:27789707). Complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) has been suggested to also act an InlB receptor, but this is less certain. Stimulation of Tyr-phosphorylation of MET by InlB is potentiated by the InlB GW domains and glycosaminoglycans such as heparin (By similarity).SUBUNIT Interacts via its LRR repeats plus the Ig-like region with the extracellular portion (residues 25-741) of its receptor MET; MET can bind HGF, its endogenous ligand, and InlB simultaneously (PubMed:17662939). Probably forms a dimer upon interaction with host MET, which subsequently allows dimerization of the host MET and subsequent host signaling; dimerization probably occurs via the convex surface of InlB (Probable) (PubMed:19900460). Prevention of dimerization does not block interaction with MET but prevents downstream action (PubMed:19900460).INTERACTION 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. Protein is 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.DOMAIN The N-terminus (36-79) resembles a truncated EF hand, the LRR region (80-240) has a curved form, while residues 241-321 form an Ig-like region; the whole region forms a curved tube (PubMed:11575932, PubMed:17662939, PubMed:19900460). The LRR domain alone (31-241) binds mammalian MET and stimulates its Tyr-phosphorylation; the LRR plus Ig-like region (36-321) are required for receptor dimerization; adding the B-repeat allows the protein to scatter host cell colonies, and the GW domains, especially GW2 and GW3, potentiate MET activation (PubMed:17662939, PubMed:21345802). The cap, LRR and Ig-like regions all interact with residues 25-656 of host MET (the Sema, PSI and Ig1 domains) via the interior (concave surface) of the curved tube (PubMed:17662939). Dimerizes via the exterior (convex surface) of the curved tube which probably induces host receptor dimerization; preventing dimerization prevents host downstream signaling (Probable) (PubMed:19900460). The B repeat region crystallizes in a SUMO-like fold. The B repeat region interacts synergistically with N-terminus of InlB, conferring on it the ability to stimulate cell motility; the B repeat does not bind to MET (PubMed:21345802). Deletion of the B-repeat (exact residues are not given) slightly decreased protein activity in host; the authors suggest the B-repeat probably contributes to homodimerization rather than binding another host cell receptor (PubMed:27789707).DISRUPTION PHENOTYPE Deletion of inlB alone decreases host cell entry; the reduction varies from 99% to 37% depending on the cell line tested.SIMILARITY Belongs to the internalin family.
created[InstanceEdit:9637754] Orlic-Milacic, Marija, 2019-02-19
descriptionrecommendedName: Internalin B shortName: InlB alternativeName: Invasion protein InlB
geneNameinlB
lmo0434
identifierP0DQD2
isSequenceChangedFALSE
keyword3D-structure
Cell membrane
Cytoplasm
Heparin-binding
Leucine-rich repeat
Lipid-binding
Membrane
Reference proteome
Repeat
Secreted
Signal
Virulence
modified[InstanceEdit:9645038] Weiser, JD
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
nameinlB
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierINLB_LISMO
P25147
Q9EXG1
sequenceLength630
species[Species:8875364] Listeria monocytogenes serovar 1/2a
(referenceEntity)[EntityWithAccessionedSequence:9637760] InlB [Gram-positive-bacterium-type cell wall] [Listeria monocytogenes]
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No pathways have been reviewed or authored by UniProt:P0DQD2 inlB (9637755)