5j1s
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/TOR1A_HUMAN 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.<ref>PMID:15505207</ref> <ref>PMID:16361107</ref> <ref>PMID:17428918</ref> <ref>PMID:18167355</ref> <ref>PMID:18827015</ref> <ref>PMID:19339278</ref> <ref>PMID:20169475</ref> <ref>PMID:23569223</ref> | [https://www.uniprot.org/uniprot/TOR1A_HUMAN 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.<ref>PMID:15505207</ref> <ref>PMID:16361107</ref> <ref>PMID:17428918</ref> <ref>PMID:18167355</ref> <ref>PMID:18827015</ref> <ref>PMID:19339278</ref> <ref>PMID:20169475</ref> <ref>PMID:23569223</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (DeltaE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the DeltaE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 A crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinADeltaE-LULL1 interaction, which enabled us to solve its structure at 1.4 A also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinADeltaE could serve as a cure for primary dystonia. | ||
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| + | Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia.,Demircioglu FE, Sosa BA, Ingram J, Ploegh HL, Schwartz TU Elife. 2016 Aug 4;5. pii: e17983. doi: 10.7554/eLife.17983. PMID:27490483<ref>PMID:27490483</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5j1s" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
TorsinA-LULL1 complex, H. sapiens, bound to VHH-BS2
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