A locally closed conformation of a bacterial pentameric proton-gated ion channel. - Institut Pasteur Access content directly
Journal Articles Nature Structural and Molecular Biology Year : 2012

A locally closed conformation of a bacterial pentameric proton-gated ion channel.

Abstract

Pentameric ligand-gated ion channels mediate signal transduction through conformational transitions between closed-pore and open-pore states. To stabilize a closed conformation of GLIC, a bacterial proton-gated homolog from Gloeobacter violaceus whose open structure is known, we separately generated either four cross-links or two single mutations. We found all six mutants to be in the same 'locally closed' conformation using X-ray crystallography, sharing most of the features of the open form but showing a locally closed pore as a result of a concerted bending of all of its M2 helices. The mutants adopt several variant conformations of the M2-M3 loop, and in all cases an interacting lipid that is observed in the open form disappears. A single cross-linked mutant is functional, according to electrophysiology, and the locally closed structure of this mutant indicates that it has an increased flexibility. Further cross-linking, accessibility and molecular dynamics data suggest that the locally closed form is a functionally relevant conformation that occurs during allosteric gating transitions.

Domains

Biophysics

Dates and versions

hal-00760125 , version 1 (03-12-2012)

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Cite

Marie S Prevost, Ludovic Sauguet, Hugues Nury, Catherine van Renterghem, Christèle Huon, et al.. A locally closed conformation of a bacterial pentameric proton-gated ion channel.. Nature Structural and Molecular Biology, 2012, 19 (6), pp.642-9. ⟨10.1038/nsmb.2307⟩. ⟨hal-00760125⟩
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