Molecular basis of V-ATPase inhibition by bafilomycin A1.

ABSTRACT: 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 translocatio

SUBMITTER: Wang R 

PROVIDER: S-EPMC7979754 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature