Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
Commun Biol. 2021 May 25;4(1):625. doi: 10.1038/s42003-021-02156-4.
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.
1,4,5-三磷酸肌醇型受体（IPR1）是神经元中主要的 Ca2+释放通道。IPR1 介导内质网向细胞质释放 Ca2+，从而参与许多生理过程。在此，我们通过单颗粒电子 cryo 显微镜在无配体、关闭状态下，展示了在存在磷脂酰胆碱的情况下，用脂质纳米盘重构成的全长大鼠 IPR1 以及去污剂溶解的结构。值得注意的是，这两种结构都表现出了确立的 IPR1 蛋白折叠，并揭示了与跨膜域结合的有序脂质的相似位置的几乎完整的脂质表示。结合脂质的结构显示出改进的特征，使我们能够明确地构建 IPR1 的原子模型，包括以前在 TM 区域中未解决的两个膜相关螺旋。我们的研究结果表明，同三聚体离子通道中蛋白结合脂质的保守位置对于其结构和功能完整性至关重要，尽管它们的门控结构机制具有多样性。
