Single-molecule FRET and molecular dynamics simulations reveal early activation steps of MET receptor by Listeria monocytogenes

  • The human growth factor receptor MET is a receptor tyrosine kinase involved in cell proliferation, migration, and survival. MET is also hijacked by the intracellular pathogen Listeria monocytogenes. Its invasion protein, internalin B (InlB), binds to MET and promotes the formation of a signaling dimer that triggers the internalization of the pathogen. Here, we use a combination of structural biology, modeling, molecular dynamics simulations, and in situ single-molecule Förster resonance energy transfer (smFRET) experiments to elucidate the early events in MET activation by Listeria. Simulations show that InlB binding stabilizes MET in a conformation that promotes dimer formation. smFRET identifies the organization of the in situ signaling dimer. Further MD simulations of the dimer model are in quantitative agreement with smFRET. We accurately describe the structural dynamics underpinning an important cellular event and introduce a powerful methodological pipeline applicable to studying the activation of other plasma membrane receptors.

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Author:Yunqing Li, Serena ArghittuORCiD, Marina DietzORCiDGND, Daniel Haße, Davide FerrarisORCiDGND, Petra Freund, Hans-Dieter Barth, Hartmut H. Niemann, Roberto CovinoORCiD, Mike HeilemannORCiDGND
URN:urn:nbn:de:hebis:30:3-830278
URL:https://www.biorxiv.org/content/10.1101/2023.12.22.572978v1
DOI:https://doi.org/10.1101/2023.12.22.572978
Parent Title (English):bioRxiv
Publisher:bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2023/12/23
Date of first Publication:2023/12/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/03/07
Tag:MET; internalin B; molecular dynamics; receptor tyrosine kinase activation; single-molecule FRET
Issue:2023.12.22.572978 Version 1
Edition:Version 1
Page Number:23
HeBIS-PPN:516889273
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-ND - Namensnennung - Keine Bearbeitungen 4.0 International