7UNE

The V1 region of bovine V-ATPase in complex with human mEAK7 (focused refinement)

これはPDB形式変換不可エントリーです。

7UNE の概要

• エントリーDOI: 10.2210/pdb7une/pdb
• EMDBエントリー: 26622
• 分子名称: V-type proton ATPase catalytic subunit A, V-type proton ATPase subunit D, KIAA1609 protein, isoform CRA_a, ... (6 entities in total)
• 機能のキーワード: proton transport, mtor signaling
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 574755.91

構造登録者

Wang, R.,Li, X. (登録日: 2022-04-10, 公開日: 2022-06-15, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.73 Å)