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

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.

SUBMITTER: Demircioglu FE 

PROVIDER: S-EPMC6646356 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature