National Natural Science Foundation of China (NSFC)
31971134
中国
引用
ジャーナル: Nat Commun / 年: 2022 タイトル: N-type fast inactivation of a eukaryotic voltage-gated sodium channel. 著者: Jiangtao Zhang / Yiqiang Shi / Junping Fan / Huiwen Chen / Zhanyi Xia / Bo Huang / Juquan Jiang / Jianke Gong / Zhuo Huang / Daohua Jiang / 要旨: Voltage-gated sodium (Na) channels initiate action potentials. Fast inactivation of Na channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing ...Voltage-gated sodium (Na) channels initiate action potentials. Fast inactivation of Na channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing frequency. Here we present cryo-electron microscopy structure of NaEh from the coccolithophore Emiliania huxleyi, which reveals an unexpected molecular gating mechanism for Na channel fast inactivation independent of the Ile-Phe-Met motif. An N-terminal helix of NaEh plugs into the open activation gate and blocks it. The binding pose of the helix is stabilized by multiple electrostatic interactions. Deletion of the helix or mutations blocking the electrostatic interactions completely abolished the fast inactivation. These strong interactions enable rapid inactivation, but also delay recovery from fast inactivation, which is ~160-fold slower than human Na channels. Together, our results provide mechanistic insights into fast inactivation of NaEh that fundamentally differs from the conventional local allosteric inhibition, revealing both surprising structural diversity and functional conservation of ion channel inactivation.
分子量: 91684.469 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Emiliania huxleyi (真核生物) / 発現宿主: Homo sapiens (ヒト)
#2: タンパク質・ペプチド
ionchannel
分子量: 1913.298 Da / 分子数: 1 / 由来タイプ: 組換発現 / 詳細: N-terminal helix of either of the four protomers / 由来: (組換発現) Emiliania huxleyi (真核生物) / 発現宿主: Homo sapiens (ヒト)