7KHR

Cryo-EM structure of bafilomycin A1-bound intact V-ATPase from bovine brain

Summary for 7KHR

• Entry DOI: 10.2210/pdb7khr/pdb
• EMDB information: 22880
• Descriptor: V-type proton ATPase catalytic subunit A, V-type proton ATPase 21 kDa proteolipid subunit, V-type proton ATPase subunit d 1, ... (25 entities in total)
• Functional Keywords: proton transport, bafilomycin a1
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 32
• Total formula weight: 1060373.81

Authors

Wang, R.,Li, X. (deposition date: 2020-10-21, release date: 2021-03-17, Last modification date: 2021-09-29)

Primary citation

Wang, R.,Wang, J.,Hassan, A.,Lee, C.H.,Xie, X.S.,Li, X.
Molecular basis of V-ATPase inhibition by bafilomycin A1.
Nat Commun, 12:1782-1782, 2021

PubMed 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 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.

PubMed: 33741963
DOI: 10.1038/s41467-021-22111-5

Experimental method

ELECTRON MICROSCOPY (3.62 Å)