TY  - INPR
A1  - Li, Yunqing
A1  - Arghittu, Serena
A1  - Dietz, Marina
A1  - Haße, Daniel
A1  - Ferraris, Davide
A1  - Freund, Petra
A1  - Barth, Hans-Dieter
A1  - Niemann, Hartmut H.
A1  - Covino, Roberto
A1  - Heilemann, Mike
T1  - Single-molecule FRET and molecular dynamics simulations reveal early activation steps of MET receptor by Listeria monocytogenes
T2  - bioRxiv
N2  - 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.
KW  - MET
KW  - receptor tyrosine kinase activation
KW  - single-molecule FRET
KW  - molecular dynamics
KW  - internalin B
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83027
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-830278
UR  - https://www.biorxiv.org/content/10.1101/2023.12.22.572978v1
IS  - 2023.12.22.572978 Version  1
PB  - bioRxiv
ER  -