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

Nat Commun. 2019 Jul 22;10(1):3262. doi: 10.1038/s41467-019-11194-w.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Models, Molecular*
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Mutation
  • Polymerization
  • Polymers / chemistry*
  • Polymers / metabolism
  • Protein Conformation*

Substances

  • Molecular Chaperones
  • Polymers
  • TOR1A protein, human
  • Adenosine Triphosphatases