Nucleotide-Specific Autoinhibition of Full-Length K-Ras4B Identified by Extensive Conformational Sampling.

ABSTRACT: K-Ras is one of the most frequently mutated oncogenes in human tumor cells. It consists of a well-conserved globular catalytic domain and a flexible tail-like hypervariable region (HVR) at its C-terminal end. It plays a key role in signaling networks in proliferation, differentiation, and survival, undergoing a conformational switch between the active and inactive states. It is regulated through the GDP-GTP cycle of the inactive GDP-bound and active GTP-bound states. Here, without imposing any prior constraints, we mapped the interaction pattern between the catalytic domain and the HVR using Molecular Dynamics with excited Normal Modes (MDeNM) starting from an initially extended HVR conformation for both states. Our sampling captured similar interaction patterns in both GDP- and GTP-bound

SUBMITTER: Dudas B 

PROVIDER: S-EPMC7366858 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature