Cryo-EM structure of type 1 IP3R channel in a lipid bilayer

Type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) is the predominant Ca2+-release channel in neurons. IP(3)R1 mediates Ca2+ 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 IP(3)R1 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 IP(3)R1 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 IP(3)R1 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. 3D structure of full-length rat type 1 inositol 1,4,5-trisphosphate receptor reconstituted in lipid nanodisc is determined using single-particle cryo-electron microscopy. The study suggests conserved locations of protein-bound lipids among structurally diverse, homo-tetrameric ion channels.

Automated summary

The study determined the 3D structure of full-length rat type 1 inositol 1,4,5-trisphosphate receptor reconstituted in lipid nanodisc using single-particle cryo-electron microscopy, suggesting conserved locations of protein-bound lipids among structurally diverse, homo-tetrameric ion channels.