{"entity": "publication", "iuid": "db0e70c3c5f549da9c966a8cf1960cce", "timestamp": "2026-08-22T07:48:35.888Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/db0e70c3c5f549da9c966a8cf1960cce.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/db0e70c3c5f549da9c966a8cf1960cce"}}, "title": "Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.", "authors": [{"family": "Rov\u0161nik", "given": "Ur\u0161ka", "initials": "U"}, {"family": "Zhuang", "given": "Yuxuan", "initials": "Y"}, {"family": "Forsberg", "given": "Bj\u00f6rn O", "initials": "BO"}, {"family": "Carroni", "given": "Marta", "initials": "M"}, {"family": "Yvonnesdotter", "given": "Linnea", "initials": "L"}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0002-2734-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9eb30fa60f9b4b95842ac9d9f3a0eaa9.json"}}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "volume": "4", "issue": "8", "issn-l": null}, "abstract": "Ligand-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 \u03b21-\u03b22 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.", "doi": "10.26508/lsa.202101011", "pmid": "34210687", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8326787"}, {"db": "pii", "key": "4/8/e202101011"}, {"db": "PDB", "key": "4NPQ"}, {"db": "PDB", "key": "4HFI"}, {"db": "PDB", "key": "6ZGD"}, {"db": "PDB", "key": "6ZGJ"}, {"db": "PDB", "key": "6ZGK"}], "notes": [], "created": "2026-08-20T13:03:57.561Z", "modified": "2026-08-20T13:03:57.592Z"}