7X5V

NaVEh Sodium channel, and NaVEh from the coccolithophore Emiliania huxleyi

Summary for 7X5V

• Entry DOI: 10.2210/pdb7x5v/pdb
• EMDB information: 33016
• Descriptor: ion channel,GFP-TwinStrep, ion channel (2 entities in total)
• Functional Keywords: ion channel, transport protein
• Biological source: Emiliania huxleyi; More
• Total number of polymer chains: 5
• Total formula weight: 368651.17

Authors

Jiang, D.,Zhang, J. (deposition date: 2022-03-05, release date: 2022-06-01, Last modification date: 2024-06-26)

Primary citation

Zhang, J.,Shi, Y.,Fan, J.,Chen, H.,Xia, Z.,Huang, B.,Jiang, J.,Gong, J.,Huang, Z.,Jiang, D.
N-type fast inactivation of a eukaryotic voltage-gated sodium channel.
Nat Commun, 13:2713-2713, 2022

PubMed Abstract: 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.

PubMed: 35581266
DOI: 10.1038/s41467-022-30400-w

Experimental method

ELECTRON MICROSCOPY (2.83 Å)