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

FE Demircioglu, W Zheng, AJ McQuown… - Nature …, 2019 - nature.com
FE Demircioglu, W Zheng, AJ McQuown, NK Maier, N Watson, IM Cheeseman, V Denic…
Nature Communications, 2019nature.com
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 …
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.
nature.com