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Publication Abstract from PubMed

The sigma-1 receptor (sigma1R) 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 sigma1R reveal its homotrimeric organization of a cupin-fold beta-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 sigma1R from Xenopus laevis. Together with functional binding analysis our data suggest that access to the sigma1R 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.

An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway.,Meng F, Xiao Y, Ji Y, Sun Z, Zhou X Nat Commun. 2022 Mar 10;13(1):1267. doi: 10.1038/s41467-022-28946-w. PMID:35273182^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.