Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 28, Issue 21, Pages 2765-2772Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E17-05-0281
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Funding
- National Institutes of Health [1R01GM114401, CMBTG T32GM007223]
- National Science Foundation GROW through the Japan Society for the Promotion of Science
- group of Mikako Shirouzu (RIKEN CLST)
- Grants-in-Aid for Scientific Research [17H05897] Funding Source: KAKEN
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TorsinA is an essential AAA+ ATPase requiring LAP1 or LULL1 as cofactors. The dynamics of the Torsin/cofactor system remain poorly understood, with previous models invoking Torsin/cofactor assemblies with fixed stoichiometries. Here we demonstrate that TorsinA assembles into homotypic oligomers in the presence of ATP. Torsin variants mutated at the back interface disrupt homo-oligomerization but still show robust ATPase activity in the presence of its cofactors. These Torsin mutants are severely compromised in their ability to rescue nuclear envelope defects in Torsin-deficient cells, suggesting that TorsinA homo-oligomers play a key role in vivo. Engagement of the oligomer by LAP1 triggers ATP hydrolysis and rapid complex disassembly. Thus the Torsin complex is a highly dynamic assembly whose oligomeric state is tightly controlled by distinctively localized cellular cofactors. Our discovery that LAP1 serves as a modulator of the oligomeric state of an AAA+ protein establishes a novel means of regulating this important class of oligomeric ATPases.
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