Free energy and flexibility analysis of autoinhibited human BRAF.

ABSTRACT: The RAF serine/threonine protein kinases function as direct effectors of RAS in the intracellular transmission of extracellular growth signals, and they are key targets for drug discovery given the high incidence of oncogenic mutations in RAF and other components of this signaling pathway. In its inactive state, RAF is held in an autoinhibited conformation in the cytosol through a combination of intramolecular interactions and binding to a regulatory 14-3-3 protein dimer. Activation of RAF is initiated by its interaction with membrane-localized, GTP-bound RAS, which induces conformational changes that release RAF from its autoinhibited state. However, the molecular mechanisms governing RAF activation remain incomplete, largely due to the challenges in experimentally capturing intermediate

SUBMITTER: Tempkin JOB 

PROVIDER: S-EPMC12340820 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature