Department of Anesthesiology

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An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel.

TitleAn iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel.
Publication TypeJournal Article
Year of Publication2018
AuthorsMarchesi A, Gao X, Adaixo R, Rheinberger J, Stahlberg H, Nimigean C, Scheuring S
JournalNat Commun
Volume9
Issue1
Pagination3978
Date Published2018 Sep 28
ISSN2041-1723
Abstract

Cyclic nucleotide-gated (CNG) ion channels are non-selective cation channels key to signal transduction. The free energy difference of cyclic-nucleotide (cAMP/cGMP) binding/unbinding is translated into mechanical work to modulate the open/closed probability of the pore, i.e., gating. Despite the recent advances in structural determination of CNG channels, the conformational changes associated with gating remain unknown. Here we examine the conformational dynamics of a prokaryotic homolog of CNG channels, SthK, using high-speed atomic force microscopy (HS-AFM). HS-AFM of SthK in lipid bilayers shows that the CNBDs undergo dramatic conformational changes during the interconversion between the resting (apo and cGMP) and the activated (cAMP) states: the CNBDs approach the membrane and splay away from the 4-fold channel axis accompanied by a clockwise rotation with respect to the pore domain. We propose that these movements may be converted by the C-linker to pull the pore helices open in an iris diaphragm-like mechanism.

DOI10.1038/s41467-018-06414-8
Alternate JournalNat Commun
PubMed ID30266906
PubMed Central IDPMC6162275
Grant List310080 / / EC | European Research Council (ERC) /
R01 GM124451 / GM / NIGMS NIH HHS / United States
R01GM124451 / / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) /
MSCA IF-2014-EF-655157 / / EC | Horizon 2020 (European Union Framework Programme for Research and Innovation) /
ALTF 1427-2014 / / European Molecular Biology Organization (EMBO) /