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==Overview== | ==Overview== | ||
The tyrosine kinase Met, the product of the c-met proto-oncogene and the | The tyrosine kinase Met, the product of the c-met proto-oncogene and the receptor for hepatocyte growth factor/scatter factor (HGF/SF), mediates signals critical for cell survival and migration. The human pathogen Listeria monocytogenes exploits Met signaling for invasion of host cells via its surface protein InlB. We present the crystal structure of the complex between a large fragment of the human Met ectodomain and the Met-binding domain of InlB. The concave face of the InlB leucine-rich repeat region interacts tightly with the first immunoglobulin-like domain of the Met stalk, a domain which does not bind HGF/SF. A second contact between InlB and the Met Sema domain locks the otherwise flexible receptor in a rigid, signaling competent conformation. Full Met activation requires the additional C-terminal domains of InlB which induce heparin-mediated receptor clustering and potent signaling. Thus, although it elicits a similar cellular response, InlB is not a structural mimic of HGF/SF. | ||
==Disease== | |||
Known diseases associated with this structure: Autism, suseptibility to, 9 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Hepatocellular carcinoma, childhood type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Renal cell carcinoma, papillary, familial and sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]] | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
Structure of the | Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB., Niemann HH, Jager V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, Gherardi E, Heinz DW, Cell. 2007 Jul 27;130(2):235-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17662939 17662939] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Listeria monocytogenes]] | [[Category: Listeria monocytogenes]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Butler, P | [[Category: Butler, P J.G.]] | ||
[[Category: Ferraris, D.]] | [[Category: Ferraris, D.]] | ||
[[Category: Gherardi, E.]] | [[Category: Gherardi, E.]] | ||
[[Category: Heinz, D | [[Category: Heinz, D W.]] | ||
[[Category: Heuvel, J | [[Category: Heuvel, J Van Den.]] | ||
[[Category: Jager, V.]] | [[Category: Jager, V.]] | ||
[[Category: Niemann, H | [[Category: Niemann, H H.]] | ||
[[Category: Schmidt, S.]] | [[Category: Schmidt, S.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
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[[Category: virulence factor]] | [[Category: virulence factor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:51:56 2008'' | ||