4aw4: Difference between revisions
New page: '''Unreleased structure''' The entry 4aw4 is ON HOLD Authors: Niemann, H.H., Heinz, D.W. Description: Engineered variant of Listeria monocytogenes InlB internalin domain with an additi... |
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The | ==Engineered variant of Listeria monocytogenes InlB internalin domain with an additional leucine rich repeat inserted== | ||
<StructureSection load='4aw4' size='340' side='right'caption='[[4aw4]], [[Resolution|resolution]] 1.93Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aw4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes_EGD-e Listeria monocytogenes EGD-e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AW4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4aw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw4 OCA], [https://pdbe.org/4aw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aw4 RCSB], [https://www.ebi.ac.uk/pdbsum/4aw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aw4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/INLB_LISMG INLB_LISMG] Mediates the entry of L.monocytogenes into normally non-phagocytic mammalian host cells (Probable) (PubMed:9282740, PubMed:11081636). 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 (PubMed:11081636, PubMed:15049825). Downstream adapter proteins GAB1 and CBL are phosphorylated in response to InlB, which also causes cell colony scattering (PubMed:11081636). InlB binding to mammalian cells is saturable and inhibited by EDTA; InlB-coated beads can be taken up by host cells (PubMed:10747014). 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 (PubMed:10747014). 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 (PubMed:15049825). 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 (PubMed:15049825). 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 (PubMed:12411480).<ref>PMID:10747014</ref> <ref>PMID:11081636</ref> <ref>PMID:12411480</ref> <ref>PMID:15049825</ref> <ref>PMID:9282740</ref> <ref>PMID:11081636</ref> <ref>PMID:1905979</ref> <ref>PMID:8864117</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The physiological relevance of contacts in crystal lattices often remains elusive. This was also the case for the complex between the invasion protein internalin B (InlB) from Listeria monocytogenes and its host cell receptor, the human receptor tyrosine kinase (RTK) MET. InlB is aMET agonist and induces bacterialhost cell invasion.Activation of RTKs generally involves ligand-induced dimerization of the receptor ectodomain. The two currently available crystal structures of the InlB:MET complex show the same arrangement of InlB and MET in a 1:1 complex, but different dimeric 2:2 assemblies. Only one of these 2:2 assemblies is predicted to be stable by a computational procedure. This assembly is mainly stabilized by a contact between the Cap domain of InlB from one and the Sema domain of MET from another 1:1 complex.Here, we probe the physiological relevance of this interaction. We generatedvariants of the leucine-rich repeat (LRR) protein InlBby inserting an additional repeat between the first and the second LRR. This should allow formation of the 1:1 complex but disrupt the potential 2:2 complex involving the Cap-Sema contact due to steric distortions. A crystal structure of oneof the engineered proteins showed that it folded properly. Binding affinityto MET was comparable to that of wild-type InlB. The InlB variant induced MET phosphorylation and cell scatter like wild-type InlB.Theseresults suggestthat the Cap-Sema interaction is not physiologically relevant and support the previously proposed assembly, in which a 2:2 InlB-MET complex is built around a ligand dimer. | |||
Engineered variants of InlB with an additional leucine-rich repeat discriminate between physiologically relevant and packing contacts in crystal structures of the InlB:MET complex.,Niemann HH, Gherardi E, Bleymuller WM, Heinz DW Protein Sci. 2012 Aug 10. doi: 10.1002/pro.2142. PMID:22887347<ref>PMID:22887347</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4aw4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Listeria monocytogenes EGD-e]] | |||
[[Category: Heinz DW]] | |||
[[Category: Niemann HH]] | |||