5J1S

TorsinA-LULL1 complex, H. sapiens, bound to VHH-BS2

5J1S の概要

• エントリーDOI: 10.2210/pdb5j1s/pdb
• 分子名称: Torsin-1A, Torsin-1A-interacting protein 2, VHH domain BS-2, ... (8 entities in total)
• 機能のキーワード: aaa+ atpase, torsin, endoplasmic reticulum, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 73580.85

構造登録者

Demircioglu, F.E.,Schwartz, T.U. (登録日: 2016-03-29, 公開日: 2016-08-17, 最終更新日: 2024-10-16)

主引用文献

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

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: 27490483
DOI: 10.7554/eLife.17983

実験手法

X-RAY DIFFRACTION (1.399 Å)