Molecular basis of mEAK7-mediated human V-ATPase regulation.

ABSTRACT: The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V₁ and V_o domains in response to growth factor stimulation, nutrient sensing, and cellular differentiation. The molecular basis of its regulation by an endogenous modulator without affecting V-ATPase assembly remains unclear. Here, we discover that a lysosome-anchored protein termed (mammalian Enhancer-of-Akt-1-7 (mEAK7)) binds to intact V-ATPase. We determine cryo-EM structure of human mEAK7 in complex with human V-ATPase in native lipid-containing nanodiscs. The structure reveals that the TLDc domain of mEAK7 engages with subunits A, B, and E, while its C-terminal domain binds to subunit D, presumably blocking V₁-V_o torque transmission. Our functional studi

SUBMITTER: Wang R 

PROVIDER: S-EPMC9174246 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature