title: Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA.
abstract: A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex.
authors: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506 USA.
authors: Hui
authors: H
authors: Li
authors: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506 USA.
authors: Hui-Chuan
authors: HC
authors: Wu
authors: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506 USA ; Department of Embryology, Carnegie Institution, Baltimore, MD 21218 USA.
authors: Zhonghua
authors: Z
authors: Liu
authors: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 USA.
authors: Lucia F
authors: LF
authors: Zacchi
authors: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 USA.
authors: Jeffrey L
authors: JL
authors: Brodsky
authors: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506 USA.
authors: Michal
authors: M
authors: Zolkiewski
keywords: AAA+ ATPase; Early-onset dystonia, TorsinA; Protein association