Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.

2.50
Hdl Handle:
http://hdl.handle.net/10033/51973
Title:
Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.
Authors:
Niemann, Hartmut H; Jäger, Volker; Butler, P Jonathan G; van den Heuvel, Joop ( 0000-0001-5085-4010 ) ; Schmidt, Sabine; Ferraris, Davide; Gherardi, Ermanno; Heinz, Dirk W
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.
Affiliation:
Division of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Citation:
Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. 2007, 130 (2):235-46 Cell
Journal:
Cell
Issue Date:
27-Jul-2007
URI:
http://hdl.handle.net/10033/51973
DOI:
10.1016/j.cell.2007.05.037
PubMed ID:
17662939
Type:
Article
Language:
en
ISSN:
0092-8674
Appears in Collections:
Publications from Division of Molekulare Struktur Biologie (MOSB)

Full metadata record

DC FieldValue Language
dc.contributor.authorNiemann, Hartmut H-
dc.contributor.authorJäger, Volker-
dc.contributor.authorButler, P Jonathan G-
dc.contributor.authorvan den Heuvel, Joop-
dc.contributor.authorSchmidt, Sabine-
dc.contributor.authorFerraris, Davide-
dc.contributor.authorGherardi, Ermanno-
dc.contributor.authorHeinz, Dirk W-
dc.date.accessioned2009-03-04T10:23:57Z-
dc.date.available2009-03-04T10:23:57Z-
dc.date.issued2007-07-27-
dc.identifier.citationStructure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. 2007, 130 (2):235-46 Cellen
dc.identifier.issn0092-8674-
dc.identifier.pmid17662939-
dc.identifier.doi10.1016/j.cell.2007.05.037-
dc.identifier.urihttp://hdl.handle.net/10033/51973-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshBacterial Proteinsen
dc.subject.meshBinding Sitesen
dc.subject.meshHeparinen
dc.subject.meshHepatocyte Growth Factoren
dc.subject.meshHumansen
dc.subject.meshListeria monocytogenesen
dc.subject.meshMembrane Proteinsen
dc.subject.meshModels, Biologicalen
dc.subject.meshModels, Molecularen
dc.subject.meshProtein Bindingen
dc.subject.meshProtein Interaction Mappingen
dc.subject.meshProtein Structure, Secondaryen
dc.subject.meshProtein Structure, Tertiaryen
dc.subject.meshProteinsen
dc.subject.meshProto-Oncogene Proteins c-meten
dc.titleStructure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.en
dc.typeArticleen
dc.contributor.departmentDivision of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.en
dc.identifier.journalCellen

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