CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel

Zachary M. James, Andrew J. Borst, Yoni Haitin, Brandon Frenz, Frank DiMaio, William N. Zagotta*, David Veesler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxylterminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood. Here we used cryoEM to determine the structure of the intact LliK CNG channel isolated from Leptospira licerasiae-which shares sequence similarity to eukaryotic CNG and HCN channels-in the presence of a saturating concentration of cAMP. A short S4-S5 linker connects nearby voltage-sensing and pore domains to produce a non-domain-swapped transmembrane architecture, which appears to be a hallmark of this channel family. We also observe major conformational changes of the LliK C-linkers and CNBDs relative to the crystal structures of isolated C-linker/CNBD fragments and the cryoEM structures of related CNG, HCN, and KCNH channels. The conformation of our LliK structure may represent a functional state of this channel family not captured in previous studies.

Original languageEnglish
Pages (from-to)4430-4435
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number17
DOIs
StatePublished - 25 Apr 2017

Funding

FundersFunder number
National Institute of Mental HealthR01MH102378
National Eye InstituteR01EY010329
National Institute of General Medical SciencesT32GM008268, P41GM103310
Simons Foundation349247
American Heart Association14CSA20380095

    Keywords

    • Allostery
    • Conformational changes
    • CryoEM
    • Cyclic nucleotide
    • Ion channel

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