7UNF

CryoEM structure of a mEAK7 bound human V-ATPase complex

This is a non-PDB format compatible entry.

Summary for 7UNF

• Entry DOI: 10.2210/pdb7unf/pdb
• EMDB information: 26623
• Descriptor: V-type proton ATPase 116 kDa subunit a 4, V-type proton ATPase subunit H, V-type proton ATPase subunit d 1, ... (22 entities in total)
• Functional Keywords: proton transport, mtor signaling
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 33
• Total formula weight: 1115115.26

Authors

Wang, R.,Li, X. (deposition date: 2022-04-10, release date: 2022-06-15, Last modification date: 2024-10-30)

Primary citation

Wang, R.,Qin, Y.,Xie, X.S.,Li, X.
Molecular basis of mEAK7-mediated human V-ATPase regulation.
Nat Commun, 13:3272-3272, 2022

PubMed Abstract: The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V and V 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 V-V torque transmission. Our functional studies suggest that mEAK7, which may act as a V-ATPase inhibitor, does not affect the activity of V-ATPase in vitro. However, overexpression of mEAK7 in HCT116 cells that stably express subunit a4 of V-ATPase represses the phosphorylation of ribosomal protein S6. Thus, this finding suggests that mEAK7 potentially links mTOR signaling with V-ATPase activity.

PubMed: 35672408
DOI: 10.1038/s41467-022-30899-z

Experimental method

ELECTRON MICROSCOPY (4.08 Å)