National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM072804
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R21NS106968
米国
Welch Foundation
AU-2014-20190330
米国
American Heart Association
18CDA34110086
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P01GM063210
米国
National Institutes of Health/National Eye Institute (NIH/NEI)
R01EY025218
米国
National Institutes of Health/National Eye Institute (NIH/NEI)
R01EY026545
米国
引用
ジャーナル: Commun Biol / 年: 2021 タイトル: Cryo-EM structure of type 1 IPR channel in a lipid bilayer. 著者: Mariah R Baker / Guizhen Fan / Alexander B Seryshev / Melina A Agosto / Matthew L Baker / Irina I Serysheva / 要旨: Type 1 inositol 1,4,5-trisphosphate receptor (IPR1) is the predominant Ca-release channel in neurons. IPR1 mediates Ca release from the endoplasmic reticulum into the cytosol and thereby is involved ...Type 1 inositol 1,4,5-trisphosphate receptor (IPR1) is the predominant Ca-release channel in neurons. IPR1 mediates Ca release from the endoplasmic reticulum into the cytosol and thereby is involved in many physiological processes. Here, we present the cryo-EM structures of full-length rat IPR1 reconstituted in lipid nanodisc and detergent solubilized in the presence of phosphatidylcholine determined in ligand-free, closed states by single-particle electron cryo-microscopy. Notably, both structures exhibit the well-established IPR1 protein fold and reveal a nearly complete representation of lipids with similar locations of ordered lipids bound to the transmembrane domains. The lipid-bound structures show improved features that enabled us to unambiguously build atomic models of IPR1 including two membrane associated helices that were not previously resolved in the TM region. Our findings suggest conserved locations of protein-bound lipids among homotetrameric ion channels that are critical for their structural and functional integrity despite the diversity of structural mechanisms for their gating.