5J1T
TorsinAdeltaE-LULL1 complex, H. sapiens, bound to VHH-BS2
Summary for 5J1T
| Entry DOI | 10.2210/pdb5j1t/pdb |
| Related | 5J1S |
| Descriptor | Torsin-1A, Torsin-1A-interacting protein 2, VHH domain BS-2, ... (8 entities in total) |
| Functional Keywords | aaa+ atpase, torsin, endoplasmic reticulum, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 73626.37 |
| Authors | Demircioglu, F.E.,Schwartz, T.U. (deposition date: 2016-03-29, release date: 2016-08-17, Last modification date: 2024-10-09) |
| Primary citation | Demircioglu, F.E.,Sosa, B.A.,Ingram, J.,Ploegh, H.L.,Schwartz, T.U. Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia. Elife, 5:-, 2016 Cited by PubMed Abstract: The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE 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 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å 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 TorsinAΔE could serve as a cure for primary dystonia. PubMed: 27490483DOI: 10.7554/eLife.17983 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.402 Å) |
Structure validation
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