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-Structure paper
タイトル | Molecular basis of mEAK7-mediated human V-ATPase regulation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 3272, Year 2022 |
掲載日 | 2022年6月7日 |
著者 | Rong Wang / Yu Qin / Xiao-Song Xie / Xiaochun Li / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:35672408 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.73 - 4.08 Å |
構造データ | EMDB-26622, PDB-7une: EMDB-26623, PDB-7unf: |
化合物 | ChemComp-ADP: ChemComp-NAG: ChemComp-POV: |
由来 |
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キーワード | PROTON TRANSPORT (プロトンポンプ) / mTOR signaling |