6zgd
GLIC pentameric ligand-gated ion channel, pH 7GLIC pentameric ligand-gated ion channel, pH 7
Structural highlights
Function[GLIC_GLOVI] Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.[1] Publication Abstract from PubMedLigand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. Biophysical and pharmacological characterization of these receptor proteins relies on high-quality structures in multiple, subtly distinct functional states. However, structural data in this family remain limited, particularly for resting and intermediate states on the activation pathway. Here, we report cryo-electron microscopy (cryo-EM) structures of the proton-activated Gloeobacter violaceus ligand-gated ion channel (GLIC) under three pH conditions. Decreased pH was associated with improved resolution and side chain rearrangements at the subunit/domain interface, particularly involving functionally important residues in the beta1-beta2 and M2-M3 loops. Molecular dynamics simulations substantiated flexibility in the closed-channel extracellular domains relative to the transmembrane ones and supported electrostatic remodeling around E35 and E243 in proton-induced gating. Exploration of secondary cryo-EM classes further indicated a low-pH population with an expanded pore. These results allow us to define distinct protonation and activation steps in pH-stimulated conformational cycling in GLIC, including interfacial rearrangements largely conserved in the pentameric channel family. Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.,Rovsnik U, Zhuang Y, Forsberg BO, Carroni M, Yvonnesdotter L, Howard RJ, Lindahl E Life Sci Alliance. 2021 Jul 1;4(8). pii: 4/8/e202101011. doi:, 10.26508/lsa.202101011. Print 2021 Aug. PMID:34210687[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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