Structural basis for allosteric coupling at the membrane-protein interface in Gloeobacter violaceus ligand-gated ion channel (GLIC).

The Journal of Biological Chemistry
Phanindra VelisettySudha Chakrapani

Abstract

Ligand binding at the extracellular domain of pentameric ligand-gated ion channels initiates a relay of conformational changes that culminates at the gate within the transmembrane domain. The interface between the two domains is a key structural entity that governs gating. Molecular events in signal transduction at the interface are poorly defined because of its intrinsically dynamic nature combined with functional modulation by membrane lipid and water vestibules. Here we used electron paramagnetic resonance spectroscopy to delineate protein motions underlying Gloeobacter violaceus ligand-gated ion channel gating in a membrane environment and report the interface conformation in the closed and the desensitized states. Extensive intrasubunit interactions were observed in the closed state that are weakened upon desensitization and replaced by newer intersubunit contacts. Gating involves major rearrangements of the interfacial loops, accompanied by reorganization of the protein-lipid-water interface. These structural changes may serve as targets for modulation of gating by lipids, alcohols, and amphipathic drug molecules.

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Citations

Mar 30, 2016·Structure·Benoist LaurentMarc Baaden
Sep 30, 2015·The Journal of General Physiology·Nicolaus SchmandtSudha Chakrapani
Mar 21, 2015·Biochimica Et Biophysica Acta·John E BaenzigerJiayin Sun
Mar 16, 2017·ELife·Anaïs MennyPierre-Jean Corringer
Mar 12, 2015·Acta Crystallographica. Section D, Biological Crystallography·Zaineb FouratiMarc Delarue
Oct 9, 2019·Nature Chemical Biology·Camille M HénaultChris Ulens
Dec 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Haidai HuMarc Delarue
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Feb 14, 2019·Chemical Reviews·Valentina CorradiD Peter Tieleman
Sep 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Marie LycksellErik Lindahl

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