7W2H

A double cysteine variant of the sigma-1 receptor from Xenopus laevis complexed with S1RA

7W2H の概要

• エントリーDOI: 10.2210/pdb7w2h/pdb
• 分子名称: Sigma non-opioid intracellular receptor 1, 4-[2-(5-methyl-1-naphthalen-2-yl-pyrazol-3-yl)oxyethyl]morpholine (2 entities in total)
• 機能のキーワード: sigma receptor, membrane receptor, s1r, ligand entry, membrane protein
• 由来する生物種: Xenopus laevis (African clawed frog)
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 609674.64

構造登録者

Meng, F.,Sun, Z.,Zhou, X. (登録日: 2021-11-23, 公開日: 2022-03-16, 最終更新日: 2023-11-29)

主引用文献

Meng, F.,Xiao, Y.,Ji, Y.,Sun, Z.,Zhou, X.
An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway.
Nat Commun, 13:1267-1267, 2022

PubMed Abstract: The sigma-1 receptor (σR) is a non-opioid transmembrane receptor which has been implicated in many diseases, including neurodegenerative disorders and cancer. After more than forty years of research, substantial progress has been made in understanding this unique receptor, yet the molecular mechanism of its ligand entry pathway remains uncertain. Published structures of human σR reveal its homotrimeric organization of a cupin-fold β-barrel body that contains the ligand binding site, a carboxy-terminal V-shaped two-helix bundle, and a single amino-terminal transmembrane helix, while simulation studies have suggested a ligand entry pathway that is generated by conformational rearrangements of the cupin-fold domain. Here, we present multiple crystal structures, including an open-like conformation, of σR from Xenopus laevis. Together with functional binding analysis our data suggest that access to the σR ligand binding site is likely achieved by protein conformational changes that involve the carboxy-terminal two-helix bundle, rather than structural changes in the cupin-fold domain.

PubMed: 35273182
DOI: 10.1038/s41467-022-28946-w

実験手法

X-RAY DIFFRACTION (3.796 Å)