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Human TorsinA can function in the yeast cytosol as a molecular chaperone

Adam, Ilectra, Jossé, Lyne, Tuite, Mick F (2017) Human TorsinA can function in the yeast cytosol as a molecular chaperone. Biochemical Journal, 474 (20). pp. 3439-3454. ISSN 0264-6021. E-ISSN 1470-8728. (doi:10.1042/BCJ20170395)

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Abstract

TorsinA (TorA) is an AAA+ ATPAse linked to dystonia type 1 (DYT1), a neurological disorder that leads to uncontrollable muscular movements. Although DYT1 is linked to a 3bp deletion in the C terminus of TorA, the biological function of TorA remains to be established. Here we use the yeast Saccharomyces cerevisiae as a tractable in vivo model to explore TorA function. We demonstrate that TorA can protect yeast cells against different forms of environmental stress and show that in the absence of the molecular disaggregase Hsp104, TorA can refold heat-denatured luciferase in vivo in an ATP-dependent manner. However, this activity requires TorA to be translocated to the cytoplasm from the ER in order to access and process cytoplasmic protein aggregates. Furthermore, mutational or chemical inactivation of the ATPase activity of TorA blocks this activity. We also find that TorA can inhibit the propagation of certain conformational variants of [ PSI +], the aggregated prion form of the endogenous Sup35 protein. Finally, we show that while cellular localisation remains unchanged in the dystonia-linked TorA mutant ?E302-303, the ability of this mutant form of TorA to protect against cellular stress and to facilitate protein refolding, is impaired, consistent with it being a loss of function mutation .

Item Type: Article
DOI/Identification number: 10.1042/BCJ20170395
Uncontrolled keywords: TorsinA / Hsp104 / yeast / molecular chaperone / prion / endoplasmic reticulum / protein folding
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Lyne Josse
Date Deposited: 28 Sep 2017 15:43 UTC
Last Modified: 14 Nov 2019 08:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/63659 (The current URI for this page, for reference purposes)
Tuite, Mick F: https://orcid.org/0000-0002-5214-540X
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