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-Structure paper
タイトル | Molecular basis of V-ATPase inhibition by bafilomycin A1. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 1782, Year 2021 |
掲載日 | 2021年3月19日 |
著者 | Rong Wang / Jin Wang / Abdirahman Hassan / Chia-Hsueh Lee / Xiao-Song Xie / Xiaochun Li / |
PubMed 要旨 | Pharmacological inhibition of vacuolar-type H-ATPase (V-ATPase) by its specific inhibitor can abrogate tumor metastasis, prevent autophagy, and reduce cellular signaling responses. Bafilomycin A1, a ...Pharmacological inhibition of vacuolar-type H-ATPase (V-ATPase) by its specific inhibitor can abrogate tumor metastasis, prevent autophagy, and reduce cellular signaling responses. Bafilomycin A1, a member of macrolide antibiotics and an autophagy inhibitor, serves as a specific and potent V-ATPases inhibitor. Although there are many V-ATPase structures reported, the molecular basis of specific inhibitors on V-ATPase remains unknown. Here, we report the cryo-EM structure of bafilomycin A1 bound intact bovine V-ATPase at an overall resolution of 3.6-Å. The structure reveals six bafilomycin A1 molecules bound to the c-ring. One bafilomycin A1 molecule engages with two c subunits and disrupts the interactions between the c-ring and subunit a, thereby preventing proton translocation. Structural and sequence analyses demonstrate that the bafilomycin A1-binding residues are conserved in yeast and mammalian species and the 7'-hydroxyl group of bafilomycin A1 acts as a unique feature recognized by subunit c. |
リンク | Nat Commun / PubMed:33741963 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.62 Å |
構造データ | EMDB-22880, PDB-7khr: |
化合物 | ChemComp-MG: ChemComp-ADP: ChemComp-WJP: ChemComp-POV: ChemComp-NAG: ChemComp-OLA: ChemComp-WEV: |
由来 |
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キーワード | PROTON TRANSPORT / bafilomycin A1 |