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bioRxiv · 10.1101/567099

The AAA+ ATPase TorsinA polymerizes into hollow tubes with a helical periodicity of 8.5 subunits per turn

Demircioglu, E.·Zheng, W.·McQuown, A. J.·Maier, N.·Watson, N.·Cheeseman, I. M.·Denic, V.·Egelman, E. H.·Schwartz, T. U.
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Abstract

TorsinA is an ER-resident AAA+ ATPase, whose single residue deletion of glutamate E303 results in the genetic neuromuscular disease primary dystonia. TorsinA is a highly unusual AAA+ ATPase in that it needs an external activator. Also, it appears not to 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 the still enigmatic function of it. We observe TorsinA to form helical filaments, which we analyzed by cryo-electron microscopy using helical reconstruction. The 4.4 [A] structure reveals long hollow tubes with a helical periodicity of 8.5 subunits per turn, and an inner cavity 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.

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Demircioglu, E., Zheng, W., McQuown, A. J., Maier, N., Watson, N., Cheeseman, I. M., Denic, V., Egelman, E. H., Schwartz, T. U.. 2019-03-04. The AAA+ ATPase TorsinA polymerizes into hollow tubes with a helical periodicity of 8.5 subunits per turn. https://doi.org/10.1101/567099

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