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

Anna R. Chase, Ethan Laudermilch, Jimin Wang, Hideki Shigematsu, Takeshi Yokoyama, Christian Schlieker

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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 homooligomers 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.

Original languageEnglish
Pages (from-to)2765-2772
Number of pages8
JournalMolecular Biology of the Cell
Issue number21
Publication statusPublished - 2017 Oct 15


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