Single-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptor in cells.

Autor: Li Y; Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 7, Frankfurt am Main, Germany., Arghittu SM; Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, Frankfurt am Main, Germany.; IMPRS on Cellular Biophysics, Max-von-Laue-Str. 3, Frankfurt am Main, Germany., Dietz MS; Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 7, Frankfurt am Main, Germany., Hella GJ; Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, Frankfurt am Main, Germany., Haße D; Department of Chemistry, Bielefeld University, Universitaetsstr. 25, Bielefeld, Germany., Ferraris DM; Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, Novara, Italy., Freund P; Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 7, Frankfurt am Main, Germany., Barth HD; Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 7, Frankfurt am Main, Germany., Iamele L; Department of Molecular Medicine, University of Pavia, Immunology and General Pathology Section, Via Ferrata 9, Pavia, Italy., de Jonge H; Department of Molecular Medicine, University of Pavia, Immunology and General Pathology Section, Via Ferrata 9, Pavia, Italy., Niemann HH; Department of Chemistry, Bielefeld University, Universitaetsstr. 25, Bielefeld, Germany., Covino R; Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, Frankfurt am Main, Germany. covino@fias.uni-frankfurt.de.; IMPRS on Cellular Biophysics, Max-von-Laue-Str. 3, Frankfurt am Main, Germany. covino@fias.uni-frankfurt.de.; Institute of Computer Science, Goethe-University Frankfurt, Robert-Mayer-Str. 11-15, Frankfurt am Main, Germany. covino@fias.uni-frankfurt.de., Heilemann M; Institute of Physical and Theoretical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 7, Frankfurt am Main, Germany. heilemann@chemie.uni-frankfurt.de.; IMPRS on Cellular Biophysics, Max-von-Laue-Str. 3, Frankfurt am Main, Germany. heilemann@chemie.uni-frankfurt.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 02; Vol. 15 (1), pp. 9486. Date of Electronic Publication: 2024 Nov 02.
DOI: 10.1038/s41467-024-53772-7
Abstrakt: Embedding of cell-surface receptors into a membrane defines their dynamics but also complicates experimental characterization of their signaling complexes. The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. It is also targeted by the pathogen Listeria monocytogenes, whose invasion protein, internalin B (InlB), binds to MET, forming a signaling dimer that triggers pathogen internalization. Here we use an integrative structural biology approach, combining molecular dynamics simulations and single-molecule Förster resonance energy transfer (smFRET) in cells, to investigate the early stages of MET activation. Our simulations show that InlB binding stabilizes MET in a conformation that promotes dimer formation. smFRET reveals that the in situ dimer structure closely resembles one of two previously published crystal structures, though with key differences. This study refines our understanding of MET activation and provides a methodological framework for studying other plasma membrane receptors.
(© 2024. The Author(s).)
Databáze: MEDLINE
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