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

Yunqing Li, Serena Arghittu, Marina S. Dietz, Daniel Haße, DAVIDE MARIA FERRARIS, Petra Freund, Hans-Dieter Barth, Hartmut H. Niemann, Roberto Covino, Mike Heilemann

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

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.

Lingua originaleInglese
RivistaNature Communications
DOI
Stato di pubblicazionePubblicato - 2024

Fingerprint

Entra nei temi di ricerca di 'Single-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptor in cells'. Insieme formano una fingerprint unica.

Cita questo