The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn.

Autor:	Demircioglu FE; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Zheng W; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA., McQuown AJ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA., Maier NK; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA., Watson N; W. M. Keck Microscopy Facility, The Whitehead Institute, Cambridge, MA, 02142, USA., Cheeseman IM; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA., Denic V; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA., Egelman EH; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA., Schwartz TU; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. tus@mit.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Jul 22; Vol. 10 (1), pp. 3262. Date of Electronic Publication: 2019 Jul 22.
DOI:	10.1038/s41467-019-11194-w
Abstrakt:	TorsinA is an ER-resident AAA + ATPase, whose deletion of glutamate E303 results in the genetic neuromuscular disease primary dystonia. TorsinA is an unusual AAA + ATPase that needs an external activator. Also, it likely does not thread a peptide substrate through a narrow central channel, in contrast to its closest structural homologs. Here, we examined the oligomerization of TorsinA to get closer to a molecular understanding of its still enigmatic function. We observe TorsinA to form helical filaments, which we analyzed by cryo-electron microscopy using helical reconstruction. The 4.4 Å structure reveals long hollow tubes with a helical periodicity of 8.5 subunits per turn, and an inner channel of ~ 4 nm diameter. We further show that the protein is able to induce tubulation of membranes in vitro, an observation that may reflect an entirely new characteristic of AAA + ATPases. We discuss the implications of these observations for TorsinA function.
Databáze:	MEDLINE
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