X-ray and Neutron Small-Angle Scattering Analysis of the Complex Formed by the Met Receptor and the Listeria monocytogenes Invasion Protein InlB
| العنوان: | 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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| المؤلفون: | Dirk W. Heinz, Hartmut H. Niemann, Maxim V. Petoukhov, Martine Moulin, Dmitri I. Svergun, Ermanno Gherardi, Michael Härtlein, Peter Timmins |
| المساهمون: | Division of Structural Biology, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. |
| المصدر: | Journal of molecular biology 377, 489-500 (2008). doi:10.1016/j.jmb.2008.01.027 Journal of Molecular Biology; Vol 377 |
| بيانات النشر: | Elsevier BV, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Models, Molecular, receptor, Protein Data Bank (RCSB PDB), Immunoglobulin domain, Proto-Oncogene Mas, chemistry [Repressor Proteins], Receptor tyrosine kinase, small-angle scattering, Structural Biology, Cricetinae, Receptor, metabolism [Repressor Proteins], 0303 health sciences, biology, Small-angle X-ray scattering, Chemistry, neutron scattering, 030302 biochemistry & molecular biology, tyrosine kinase, Solutions, genetics [Membrane Proteins], Ectodomain, Hepatocyte growth factor, genetics [Bacterial Proteins], Protein Binding, medicine.drug, genetics [Listeria monocytogenes], chemistry [Bacterial Proteins], metabolism [Bacterial Proteins], Stereochemistry, CHO Cells, 03 medical and health sciences, Cricetulus, Bacterial Proteins, inlB protein, Listeria monocytogenes, complex formation, ddc:570, Scattering, Small Angle, medicine, Animals, chemistry [Membrane Proteins], rigid-body modeling, Protein Structure, Quaternary, Molecular Biology, 030304 developmental biology, Neutrons, Binding Sites, Ligand, X-Rays, Membrane Proteins, Listeria monocytogenes, metabolism [Listeria monocytogenes], Repressor Proteins, genetics [Repressor Proteins], chemistry [Listeria monocytogenes], Biophysics, biology.protein, methionine repressor protein, Bacteria, metabolism [Membrane Proteins] |
| الوصف: | The Listeria monocytogenes surface protein InIB 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 InIB (InlB(321)) is sufficient for Met binding and activation. The complex between this Met-binding domain of InIB 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 InIB 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. (C) 2008 Elsevier Ltd. All rights reserved. |
| تدمد: | 0022-2836 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a9899cfd085762bd3866286fce0e837Test https://doi.org/10.1016/j.jmb.2008.01.027Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6a9899cfd085762bd3866286fce0e837 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222836 |
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