X-ray and neutron small-angle scattering analysis of the complex formed by the Met receptor and the Listeria monocytogenes invasion protein InlB.
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AuthorsNiemann, Hartmut H
Petoukhov, Maxim V
Heinz, Dirk W
Svergun, Dmitri I
MetadataShow full item record
AbstractThe Listeria monocytogenes surface protein InlB binds to the extracellular domain of the human receptor tyrosine kinase Met, the product of the c-met proto-oncogene. InlB binding activates the Met receptor, leading to uptake of Listeria into normally nonphagocytic host cells. The N-terminal half of InlB (InlB(321)) is sufficient for Met binding and activation. The complex between this Met-binding domain of InlB and various constructs of the Met ectodomain was characterized by size exclusion chromatography and dynamic light scattering, and structural models were built using small-angle X-ray scattering and small-angle neutron scattering. Although most receptor tyrosine kinase ligands induce receptor dimerization, InlB(321) consistently binds the Met ectodomain with a 1:1 stoichiometry. A construct comprising the Sema and PSI domains of Met, although sufficient to bind the physiological Met ligand hepatocyte growth factor/scatter factor, does not form a complex with InlB(321) in solution, highlighting the importance of Met Ig domains for InlB binding. Small-angle X-ray scattering and small-angle neutron scattering measurements of ligand and receptor, both free and in complex, reveal an elongated shape for the receptor. The four Ig domains form a bent, rather than a fully extended, conformation, and InlB(321) binds to Sema and the first Ig domain of Met, in agreement with the recent crystal structure of a smaller Met fragment in complex with InlB(321). These results call into question whether receptor dimerization is the basic underlying event in InlB(321)-mediated Met activation and demonstrate differences in the mechanisms by which the physiological ligand hepatocyte growth factor/scatter factor and InlB(321) bind and activate the Met receptor.
CitationX-ray and neutron small-angle scattering analysis of the complex formed by the Met receptor and the Listeria monocytogenes invasion protein InlB. 2008, 377 (2):489-500 J. Mol. Biol.
AffiliationDivision of Structural Biology, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
JournalJournal of molecular biology
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- Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.
- Authors: Niemann HH, Jäger V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, Gherardi E, Heinz DW
- Issue date: 2007 Jul 27
- Ligand-mediated dimerization of the Met receptor tyrosine kinase by the bacterial invasion protein InlB.
- Authors: Ferraris DM, Gherardi E, Di Y, Heinz DW, Niemann HH
- Issue date: 2010 Jan 22
- GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.
- Authors: Banerjee M, Copp J, Vuga D, Marino M, Chapman T, van der Geer P, Ghosh P
- Issue date: 2004 Apr
- Structural basis of MET receptor dimerization by the bacterial invasion protein InlB and the HGF/SF splice variant NK1.
- Authors: Niemann HH
- Issue date: 2013 Oct
- Fold and function of the InlB B-repeat.
- Authors: Ebbes M, Bleymüller WM, Cernescu M, Nölker R, Brutschy B, Niemann HH
- Issue date: 2011 Apr 29