N-type fast inactivation of a eukaryotic voltage-gated sodium channel

Jiangtao Zhang, Yiqiang Shi, Junping Fan, Huiwen Chen, Zhanyi Xia, Bo Huang, Juquan Jiang, Jianke Gong (), Zhuo Huang () and Daohua Jiang ()
Additional contact information
Jiangtao Zhang: Huazhong University of Science and Technology
Yiqiang Shi: Peking University Health Science Center
Junping Fan: Peking University
Huiwen Chen: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Zhanyi Xia: Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences
Bo Huang: Beijing StoneWise Technology Co Ltd.
Juquan Jiang: College of Life Sciences, Northeast Agricultural University
Jianke Gong: Huazhong University of Science and Technology
Zhuo Huang: Peking University Health Science Center
Daohua Jiang: Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Voltage-gated sodium (NaV) channels initiate action potentials. Fast inactivation of NaV 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 NaVEh from the coccolithophore Emiliania huxleyi, which reveals an unexpected molecular gating mechanism for NaV channel fast inactivation independent of the Ile-Phe-Met motif. An N-terminal helix of NaVEh 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 NaV channels. Together, our results provide mechanistic insights into fast inactivation of NaVEh that fundamentally differs from the conventional local allosteric inhibition, revealing both surprising structural diversity and functional conservation of ion channel inactivation.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30400-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30400-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30400-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().