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Mol Biol Cell. 2017 Oct 15;28(21):2765-2772. doi: 10.1091/mbc.E17-05-0281. Epub 2017 Aug 16.

Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1.

Author information

1
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520.
2
RIKEN Center for Life Science Technologies, Yokohama 230-0045, Japan.
3
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520 christian.schlieker@yale.edu.
4
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.

Abstract

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.

PMID:
28814508
PMCID:
PMC5638581
DOI:
10.1091/mbc.E17-05-0281
[Indexed for MEDLINE]
Free PMC Article

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