6oif

Cryo-EM structure of human TorsinA filament

Loading... Status: waiting for Mol* initialization Structural highlights 6oif is a 25 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP Gene: TOR1A, DQ2, DYT1, TA, TORA (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [TOR1A_HUMAN] Myoclonus-dystonia syndrome;Early-onset generalized limb-onset dystonia. The disease is caused by mutations affecting the gene represented in this entry. Function [TOR1A_HUMAN] Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non-neural tissues. Publication Abstract from PubMed 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 A 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. The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn.,Demircioglu FE, Zheng W, McQuown AJ, Maier NK, Watson N, Cheeseman IM, Denic V, Egelman EH, Schwartz TU Nat Commun. 2019 Jul 22;10(1):3262. doi: 10.1038/s41467-019-11194-w. PMID:31332180 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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