TY - JOUR
T1 - Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1
AU - Chase, Anna R.
AU - Laudermilch, Ethan
AU - Wang, Jimin
AU - Shigematsu, Hideki
AU - Yokoyama, Takeshi
AU - Schlieker, Christian
N1 - Funding Information:
This work was supported by the National Institutes of Health (1R01GM114401 to C.S. and CMBTG T32GM007223 to E.L.) and in part by a National Science Foundation GROW award through the Japan Society for the Promotion of Science to A.R.C. for work conducted at the RIKEN Center for Life Science Technologies (CLST). We thank Tomomi Uchikubo-Kamo for help with sample preparation and the group of Mikako Shirouzu (RIKEN CLST) for their support.
Publisher Copyright:
© 2017 Schvartz et al.
PY - 2017/10/15
Y1 - 2017/10/15
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E17-05-0281
DO - 10.1091/mbc.E17-05-0281
M3 - Article
C2 - 28814508
AN - SCOPUS:85031294316
SN - 1059-1524
VL - 28
SP - 2765
EP - 2772
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 21
ER -