Membrane-bound KRAS approximates an entropic ensemble of configurations.
Biophys J
; 120(18): 4055-4066, 2021 09 21.
Article
em En
| MEDLINE
| ID: mdl-34384763
ABSTRACT
KRAS4B is a membrane-anchored signaling protein and a primary target in cancer research. Predictions from molecular dynamics simulations that have previously shaped our mechanistic understanding of KRAS signaling disagree with recent experimental results from neutron reflectometry, NMR, and thermodynamic binding studies. To gain insight into these discrepancies, we compare this body of biophysical data to back-calculated experimental results from a series of molecular simulations that implement different subsets of molecular interactions. Our results show that KRAS4B approximates an entropic ensemble of configurations at model membranes containing 30% phosphatidylserine lipids, which is not significantly shaped by interactions between the globular G-domain of KRAS4B and the lipid membrane. These findings revise our understanding of KRAS signaling and promote a model in which the protein samples the accessible conformational space in a near-uniform manner while being available to bind to effector proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2021
Tipo de documento:
Article