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Crystal structure of yeast V 1 ‐ ATP ase in the autoinhibited state
Author(s) -
Oot Rebecca A,
Kane Patricia M,
Berry Edward A,
Wilkens Stephan
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593447
Subject(s) - biology , protein subunit , yeast , saccharomyces cerevisiae , organelle , cytosol , biochemistry , extracellular , adenosine triphosphate , atpase , biophysics , active site , microbiology and biotechnology , enzyme , gene
Vacuolar ATP ases (V‐ ATP ases) are essential proton pumps that acidify the lumen of subcellular organelles in all eukaryotic cells and the extracellular space in some tissues. V‐ ATP ase activity is regulated by a unique mechanism referred to as reversible disassembly, wherein the soluble catalytic sector, V 1 , is released from the membrane and its Mg ATP ase activity silenced. The crystal structure of yeast V 1 presented here shows that activity silencing involves a large conformational change of subunit H, with its C‐terminal domain rotating ~150° from a position near the membrane in holo V‐ ATP ase to a position at the bottom of V 1 near an open catalytic site. Together with biochemical data, the structure supports a mechanistic model wherein subunit H inhibits ATP ase activity by stabilizing an open catalytic site that results in tight binding of inhibitory ADP at another site.