7U4T

Human V-ATPase in state 2 with SidK and mEAK-7

This is a non-PDB format compatible entry.

Summary for 7U4T

• Entry DOI: 10.2210/pdb7u4t/pdb
• Related: 6WM3
• EMDB information: 26334
• Descriptor: V-type proton ATPase 116 kDa subunit a isoform 1, V-type proton ATPase 16 kDa proteolipid subunit, V-type proton ATPase subunit d 1, ... (20 entities in total)
• Functional Keywords: v-atpase, meak-7, membrane protein
• Biological source: Legionella pneumophila; More
• Total number of polymer chains: 36
• Total formula weight: 1302060.01

Authors

Wang, L.,Fu, T.M. (deposition date: 2022-03-01, release date: 2022-08-24, Last modification date: 2025-05-14)

Primary citation

Wang, L.,Wu, D.,Robinson, C.V.,Fu, T.M.
Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining.
Proc.Natl.Acad.Sci.USA, 119:e2203742119-e2203742119, 2022

PubMed Abstract: Vacuolar-type adenosine triphosphatases (V-ATPases) not only function as rotary proton pumps in cellular organelles but also serve as signaling hubs. To identify the endogenous binding partners of V-ATPase, we collected a large dataset of human V-ATPases and did extensive classification and focused refinement of human V-ATPases. Unexpectedly, about 17% of particles in state 2 of human V-ATPases display additional density with an overall resolution of 3.3 Å. Structural analysis combined with artificial intelligence modeling enables us to identify this additional density as mEAK-7, a protein involved in mechanistic target of rapamycin (mTOR) signaling in mammals. Our structure shows that mEAK-7 interacts with subunits A, B, D, and E of V-ATPases in state 2. Thus, we propose that mEAK-7 may regulate V-ATPase function through binding to V-ATPases in state 2 as well as mediate mTOR signaling.

PubMed: 35994636
DOI: 10.1073/pnas.2203742119

Experimental method

ELECTRON MICROSCOPY (3.6 Å)