The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn
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s41467-019-11194-w.pdf
Description
Published version
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3.32 MB
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Checksum (MD5)
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Author(s)
Demircioglu, Fatma Esra
Zheng, Weili
McQuown, Alexander J.
Maier, Nolan K.
Watson, Nicki
Denic, Vladimir
Egelman, Edward H.
Schwartz, Thomas
Cheeseman, Iain M
Date Issued
July 2019
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Demircioglu, F. Esra et al. "The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn." Nature Communications 10, 1 (July 2019): 3262 © 2019 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-019-11194-w
