Coordinated conformational changes in the V 1 complex during V-ATPase reversible dissociation
Vacuolar-type ATPases (V-ATPases) are rotary enzymes that acidify intracellular compartments in eukaryotic cells. These multi-subunit complexes consist of a cytoplasmic V region that hydrolyzes ATP and a membrane-embedded V region that transports protons. V-ATPase activity is regulated by reversible...
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Published in | Nature structural & molecular biology Vol. 29; no. 5; p. 430 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.05.2022
|
Online Access | Get full text |
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Summary: | Vacuolar-type ATPases (V-ATPases) are rotary enzymes that acidify intracellular compartments in eukaryotic cells. These multi-subunit complexes consist of a cytoplasmic V
region that hydrolyzes ATP and a membrane-embedded V
region that transports protons. V-ATPase activity is regulated by reversible dissociation of the two regions, with the isolated V
and V
complexes becoming autoinhibited on disassembly and subunit C subsequently detaching from V
. In yeast, assembly of the V
and V
regions is mediated by the regulator of the ATPase of vacuoles and endosomes (RAVE) complex through an unknown mechanism. We used cryogenic-electron microscopy of yeast V-ATPase to determine structures of the intact enzyme, the dissociated but complete V
complex and the V
complex lacking subunit C. On separation, V
undergoes a dramatic conformational rearrangement, with its rotational state becoming incompatible for reassembly with V
. Loss of subunit C allows V
to match the rotational state of V
, suggesting how RAVE could reassemble V
and V
by recruiting subunit C. |
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ISSN: | 1545-9985 |