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Activated human Orai1 channel in lipid biolayer may exist as a pentamer.

Authors :: Lu X
Wang Y
Yu K
Li M
Yang X
Shen Y
Source :: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 12; Vol. 733, pp. 150723. Date of Electronic Publication: 2024 Sep 21.
Publication Year :: 2024
Abstract: The human Orai1 (hOrai1) channel plays a crucial role in extracellular Ca <superscript>2+</superscript> influx and has emerged as an attractive drug target for various diseases. However, the activated structure of the hOrai1 channel assembly within a lipid bilayer remains unknown. In this study, we expressed and purified the hOrai1 channel covalently linked to two SOAR tandems (HOSS). Patch-clamp experiments in whole-cell configuration showed that HOSS is constitutively active. Biochemical characterization confirmed that the purified HOSS channels were successfully incorporated into MSP1E3D1 nanodiscs. Negative staining revealed that the HOSS channels resemble a mushroom, with the body representing the hOrai1 channel and the leg representing the SOAR domain. Surprisingly, 2D analysis of cryo-EM data demonstrated a pentameric assembly of HOSS in a lipid bilayer. Our findings suggest that the hOrai1 channel may assemble into different oligomeric states in response to varying membrane environments.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)