Unknown

Dataset Information

0

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


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.

SUBMITTER: Chase AR 

PROVIDER: S-EPMC5638581 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Chase Anna R AR   Laudermilch Ethan E   Wang Jimin J   Shigematsu Hideki H   Yokoyama Takeshi T   Schlieker Christian C  

Molecular biology of the cell 20170816 21


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 severe  ...[more]

Similar Datasets

| S-EPMC7773337 | biostudies-literature
| S-EPMC4358337 | biostudies-literature
| S-EPMC3637692 | biostudies-literature
| S-EPMC2836958 | biostudies-literature
| S-EPMC4234599 | biostudies-literature
2009-10-01 | GSE12279 | GEO
| S-EPMC6355894 | biostudies-literature
| S-EPMC9437592 | biostudies-literature
| S-EPMC6917787 | biostudies-literature
| S-EPMC2441676 | biostudies-literature