Conserved allosteric perturbation of the GTPase domains by region 1 of Ras hypervariable regions.

ABSTRACT: Ras proteins are important intracellular signaling hubs that can interact with numerous downstream effectors and upstream regulators through their GTPase domains (G-domains) anchored to plasma membranes by the C-terminal hypervariable regions (HVRs). The biological functions of Ras were proposed to be regulated at multiple levels including the intramolecular G-domain-HVR interactions, of which the exact mechanism and specificity are still controversial. Here, we demonstrate that the HVRs, instead of having direct contacts, can weakly perturb the G-domains via an allosteric interaction that is restricted to a ∼20 Å range and highly conserved in the tested Ras isoforms (HRas and KRas4B) and nucleotide-bound states. The origin of this allosteric perturbation has been localized to a short segm

SUBMITTER: Gu X 

PROVIDER: S-EPMC10995424 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature