{"entity": "researcher", "timestamp": "2026-08-22T06:58:39.606Z", "family": "Nimigean", "given": "Crina M", "initials": "CM", "orcid": "0000-0002-6254-4447", "affiliations": ["Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA. crn2002@med.cornell.edu.", "Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA. crn2002@med.cornell.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e75571e2b98464ca45504dabe307081.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e75571e2b98464ca45504dabe307081"}}, "publications": [{"entity": "publication", "iuid": "2e109b479efc44a88a051a343eaba0b6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2e109b479efc44a88a051a343eaba0b6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2e109b479efc44a88a051a343eaba0b6"}}, "title": "Calcium-gated potassium channel blockade via membrane-facing fenestrations.", "authors": [{"family": "Fan", "given": "Chen", "initials": "C"}, {"family": "Flood", "given": "Emelie", "initials": "E", "orcid": "0000-0002-1981-9636", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf975e0fdbe440108a20df1637a61dab.json"}}, {"family": "Sukomon", "given": "Nattakan", "initials": "N", "orcid": "0000-0002-8443-9533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ffb428dec00a41cd84667092cc27bdf8.json"}}, {"family": "Agarwal", "given": "Shubhangi", "initials": "S"}, {"family": "Allen", "given": "Toby W", "initials": "TW", "orcid": "0000-0002-3521-7950", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f3792457d97f42adaee2c2563a218ea2.json"}}, {"family": "Nimigean", "given": "Crina M", "initials": "CM", "orcid": "0000-0002-6254-4447", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e75571e2b98464ca45504dabe307081.json"}}], "type": "journal article", "published": "2024-01-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "20", "issue": "1", "pages": "52-61", "issn-l": "1552-4450"}, "abstract": "Quaternary ammonium blockers were previously shown to bind in the pore to block both open and closed conformations of large-conductance calcium-activated potassium (BK and MthK) channels. Because blocker entry was assumed through the intracellular entryway (bundle crossing), closed-pore access suggested that the gate was not at the bundle crossing. Structures of closed MthK, a Methanobacterium thermoautotrophicum homolog of BK channels, revealed a tightly constricted intracellular gate, leading us to investigate the membrane-facing fenestrations as alternative pathways for blocker access directly from the membrane. Atomistic free energy simulations showed that intracellular blockers indeed access the pore through the fenestrations, and a mutant channel with narrower fenestrations displayed no closed-state TPeA block at concentrations that blocked the wild-type channel. Apo BK channels display similar fenestrations, suggesting that blockers may use them as access paths into closed channels. Thus, membrane fenestrations represent a non-canonical pathway for selective targeting of specific channel conformations, opening novel ways to selectively drug BK channels.", "doi": "10.1038/s41589-023-01406-2", "pmid": "37653172", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1935574"}, {"db": "pmc", "key": "PMC10847966"}, {"db": "pii", "key": "10.1038/s41589-023-01406-2"}, {"db": "PDB", "key": "8FZ7"}, {"db": "PDB", "key": "5BKI"}, {"db": "PDB", "key": "5BKJ"}, {"db": "PDB", "key": "5BKK"}, {"db": "PDB", "key": "8DJB"}], "notes": [], "created": "2026-08-21T11:51:59.896Z", "modified": "2026-08-21T11:52:00.082Z"}, {"entity": "publication", "iuid": "8356325df76d47c18ae4293418c54d71", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8356325df76d47c18ae4293418c54d71.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8356325df76d47c18ae4293418c54d71"}}, "title": "Gating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel.", "authors": [{"family": "Gao", "given": "Xiaolong", "initials": "X"}, {"family": "Schmidpeter", "given": "Philipp A M", "initials": "PAM", "orcid": "0000-0003-2871-9706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b081571b22944cbb1d9349270114baa.json"}}, {"family": "Berka", "given": "Vladimir", "initials": "V"}, {"family": "Durham", "given": "Ryan J", "initials": "RJ"}, {"family": "Fan", "given": "Chen", "initials": "C"}, {"family": "Jayaraman", "given": "Vasanthi", "initials": "V"}, {"family": "Nimigean", "given": "Crina M", "initials": "CM", "orcid": "0000-0002-6254-4447", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e75571e2b98464ca45504dabe307081.json"}}], "type": "journal article", "published": "2022-11-14", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "6919", "issn-l": "2041-1723"}, "abstract": "Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the intracellular gate, pointing to an inhibitory VSD at rest. We propose that in wild-type SthK, depolarization leads to such VSD displacements resulting in release of inhibition. In summary, we report conformational transitions along the activation pathway that reveal allosteric couplings between key sites integrating to open the intracellular gate.", "doi": "10.1038/s41467-022-34673-z", "pmid": "36376326", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9663499"}, {"db": "pii", "key": "10.1038/s41467-022-34673-z"}], "notes": [], "created": "2026-08-21T11:49:16.262Z", "modified": "2026-08-21T11:49:16.390Z"}]}