The structural heterogeneity of AKT autoinhibition.

ABSTRACT: AKT is key to controlling cell growth through the PI3K/AKT/mTOR pathway. In the cytosol, in the absence of stimulus, AKT is autoinhibited to prevent uncontrolled activation. Increased AKT activity contributes to tumor growth by phosphorylating numerous downstream targets. Relieving the autoinhibition is a prerequisite for full activation, which occurs through C-terminal tail phosphorylation by mTOR, followed by activation loop phosphorylation by PDK1. However, the atomic-level mechanisms by which AKT autoinhibition persists in the cytosol and the phosphorylation (posttranslational modifications) allosterically shift AKT to its open conformation, which may serve as drug targets, remain unclear. Here, we performed explicit molecular dynamics simulations to explore the conformational ensemble

SUBMITTER: Xu L 

PROVIDER: S-EPMC12724016 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature