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Oxidative stress protein Oxr1 promotes V-ATPase holoenzyme disassembly in catalytic activity-independent manner
Cited 15 time in
Web of Science
Cited 18 time in Scopus
- Authors
- Issue Date
- 2022-02
- Publisher
- Nature Publishing Group
- Citation
- EMBO Journal, Vol.41 No.3, p. e109360
- Abstract
- The vacuolar ATPase (V-ATPase) is a rotary motor proton pump that is regulated by an assembly equilibrium between active holoenzyme and autoinhibited V-1-ATPase and V-o proton channel subcomplexes. Here, we report cryo-EM structures of yeast V-ATPase assembled in vitro from lipid nanodisc reconstituted V-o and mutant V-1. Our analysis identified holoenzymes in three active rotary states, indicating that binding of V-1 to V-o provides sufficient free energy to overcome V-o autoinhibition. Moreover, the structures suggest that the unequal spacing of V-o's proton-carrying glutamic acid residues serves to alleviate the symmetry mismatch between V-1 and V-o motors, a notion that is supported by mutagenesis experiments. We also uncover a structure of free V-1 bound to Oxr1, a conserved but poorly characterized factor involved in the oxidative stress response. Biochemical experiments show that Oxr1 inhibits V-1-ATPase and causes disassembly of the holoenzyme, suggesting that Oxr1 plays a direct role in V-ATPase regulation.
- ISSN
- 0261-4189
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