{"entity": "researcher", "timestamp": "2026-08-22T06:57:19.055Z", "family": "Tang", "given": "Pei", "initials": "P", "orcid": "0000-0002-2869-2737", "affiliations": ["Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.", "Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.", "Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f303079f5941dc83ac2e8943d62893.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f303079f5941dc83ac2e8943d62893"}}, "publications": [{"entity": "publication", "iuid": "0c73c3d0a3f34717b7f881e8cd264114", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0c73c3d0a3f34717b7f881e8cd264114.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0c73c3d0a3f34717b7f881e8cd264114"}}, "title": "Structural Elucidation of Ivermectin Binding to \u03b17nAChR and the Induced Channel Desensitization.", "authors": [{"family": "Bondarenko", "given": "Vasyl", "initials": "V"}, {"family": "Chen", "given": "Qiang", "initials": "Q"}, {"family": "Singewald", "given": "Kevin", "initials": "K"}, {"family": "Haloi", "given": "Nandan", "initials": "N"}, {"family": "Tillman", "given": "Tommy S", "initials": "TS"}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Xu", "given": "Yan", "initials": "Y"}, {"family": "Tang", "given": "Pei", "initials": "P", "orcid": "0000-0002-2869-2737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f303079f5941dc83ac2e8943d62893.json"}}], "type": "journal article", "published": "2023-03-15", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "14", "issue": "6", "pages": "1156-1165", "issn-l": "1948-7193"}, "abstract": "The \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR) mediates signaling in the central nervous system and cholinergic anti-inflammatory pathways. Ivermectin is a positive allosteric modulator of a full-length \u03b17nAChR and an agonist of the \u03b17nAChR construct containing transmembrane (TMD) and intracellular (ICD) domains, but structural insights of the binding have not previously been determined. Here, combining nuclear magnetic resonance as a primary experimental tool with Rosetta comparative modeling and molecular dynamics simulations, we have revealed details of ivermectin binding to the \u03b17nAChR TMD + ICD and corresponding structural changes in an ivermectin-induced desensitized state. Ivermectin binding was stabilized predominantly by hydrophobic interactions from interfacial residues between adjacent subunits near the extracellular end of the TMD, where the inter-subunit gap was substantially expanded in comparison to the apo structure. The ion-permeation pathway showed a profile distinctly different from the resting-state profile but similar to profiles of desensitized \u03b17nAChR. The ICD also exhibited structural changes, including reorientation of the MX and h3 helices relative to the channel axis. The resulting structures of the \u03b17nAChR TMD + ICD in complex with ivermectin provide opportunities for discovering new modulators of therapeutic potential and exploring the structural basis of cytoplasmic signaling under different \u03b17nAChR functional states.", "doi": "10.1021/acschemneuro.2c00783", "pmid": "36821490", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10020961"}], "notes": [], "created": "2026-08-20T08:09:09.725Z", "modified": "2026-08-21T11:35:55.644Z"}, {"entity": "publication", "iuid": "b9c2bc90f8d54df2ac7f08a044070041", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b9c2bc90f8d54df2ac7f08a044070041.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b9c2bc90f8d54df2ac7f08a044070041"}}, "title": "Structures of highly flexible intracellular domain of human \u03b17 nicotinic acetylcholine receptor.", "authors": [{"family": "Bondarenko", "given": "Vasyl", "initials": "V", "orcid": "0000-0002-4895-3447", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1107c602ba324a6cbbb0f4bce82bf777.json"}}, {"family": "Wells", "given": "Marta M", "initials": "MM", "orcid": "0000-0001-6800-134X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06ca900c0c9b48da8fc3d9280f0bb4e1.json"}}, {"family": "Chen", "given": "Qiang", "initials": "Q", "orcid": "0000-0002-6524-9849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9ced131179d4f45bc7ba22c0678d243.json"}}, {"family": "Tillman", "given": "Tommy S", "initials": "TS"}, {"family": "Singewald", "given": "Kevin", "initials": "K", "orcid": "0000-0002-3041-5085", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/228ac97805604b5ea7d86727adab68e0.json"}}, {"family": "Lawless", "given": "Matthew J", "initials": "MJ"}, {"family": "Caporoso", "given": "Joel", "initials": "J"}, {"family": "Brandon", "given": "Nicole", "initials": "N", "orcid": "0000-0002-3015-7741", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f957f65eed844217a529e8c17571ee37.json"}}, {"family": "Coleman", "given": "Jonathan A", "initials": "JA", "orcid": "0000-0003-0001-6195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/42a317df948b4f09a7959996141ae673.json"}}, {"family": "Saxena", "given": "Sunil", "initials": "S", "orcid": "0000-0001-9098-6114", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/46417084a7664741bcbd6ccb47b42b2a.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Xu", "given": "Yan", "initials": "Y", "orcid": "0000-0003-2773-8024", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dcaa3432b3eb4b93a6fafbb8e00820a2.json"}}, {"family": "Tang", "given": "Pei", "initials": "P", "orcid": "0000-0002-2869-2737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f303079f5941dc83ac2e8943d62893.json"}}], "type": "journal article", "published": "2022-02-10", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "793", "issn-l": "2041-1723"}, "abstract": "The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human \u03b17 nicotinic acetylcholine receptor in a resting state. We show that ~57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning ~50 \u00c5 from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.", "doi": "10.1038/s41467-022-28400-x", "pmid": "35145092", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8831596"}, {"db": "pii", "key": "10.1038/s41467-022-28400-x"}], "notes": [], "created": "2026-08-20T08:51:48.527Z", "modified": "2026-08-20T08:51:48.943Z"}]}