@article{1151791fa2774708a4e32feab1d664a1,
title = "Structure of the Human Receptor Tyrosine Kinase Met in Complex with the Listeria Invasion Protein InlB",
abstract = "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.",
keywords = "CELLBIO, HUMDISEASE, SIGNALING",
author = "Niemann, {Hartmut H.} and Volker J{\"a}ger and Butler, {P. Jonathan G.} and {van den Heuvel}, Joop and Sabine Schmidt and Davide Ferraris and Ermanno Gherardi and Heinz, {Dirk W.}",
note = "Funding Information: Initial diffraction experiments were carried out at the Protein Structure Factory beamline BL14.1 of BESSY and Free University Berlin at BESSY. We acknowledge the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities, and we would like to thank David Flot for assistance in using beamline ID23-2. We are grateful to Malcolm Lyon (Paterson Institute for Cancer Research, University of Manchester) for providing dp12 heparin and to Wolf-Dieter Schubert for helpful discussions. We would like to thank Professor Walter Birchmeier (MDC Berlin) for promoting the first contacts between the labs of E.G. and D.W.H. This work was supported in part by Deutsche Forschungsgemeinschaft Priority Program SPP1150 (to H.H.N.), MRC Programme Grant G9704528 and Grant ARC1220 by the British Council (to E.G.), and a Marie Curie Early Stage Training (EST) of the European Community's Sixth Framework Programme under contract number MEST-2004-504990 (to D.F.). E.G. also has a part-time teaching appointment at the University of Pavia (Italy), and D.W.H. acknowledges support from the Fonds der Chemischen Industrie. ",
year = "2007",
month = jul,
day = "27",
doi = "10.1016/j.cell.2007.05.037",
language = "English",
volume = "130",
pages = "235--246",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "2",
}