{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:14:21Z","timestamp":1788545661237,"version":"build-2803163510"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL159711"],"award-info":[{"award-number":["HL159711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AT012544"],"award-info":[{"award-number":["AT012544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-GM150272"],"award-info":[{"award-number":["R01-GM150272"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL159711"],"award-info":[{"award-number":["HL159711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AT012544"],"award-info":[{"award-number":["AT012544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>\n                    Most voltage-gated potassium (Kv) channels are inhibited by peptide neurotoxins that occlude the pore with a positively-charged lysine. Kv1.5 repels these toxins electrostatically via four arginines (R487), one on each pore-forming subunit. Here, we describe chimera toxin (CmTx), a potent and selective blocker that prefers the slow-inactivated Kv1.5 conformation promoted by rapid firing and acidosis (\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    \u00a0=\u00a0127 nM), conditions associated with atrial fibrillation and ischemia. CmTx was isolated by cell-based, phage-display library panning of de novo peptides engineered on a SAK1 scaffold and shows minimal inhibition of seven other Kv subtypes. Scanning mutagenesis identified CmTx and Kv1.5 residues essential to binding. AlphaFold modeling shows how acidic CmTx residues can neutralize the channel arginines, enabling one peptide to plug the Kv1.5 pore. These findings present an electrostatic pore-blocking mechanism driven by complementary charge interactions and offer CmTx as a tool to probe Kv1.5 physiology and a potential therapeutic lead.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef6020","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:58:46Z","timestamp":1788544726000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A designer pore-blocking peptide reveals an electrostatic complementation mechanism for the inhibition-resistant Kv1.5 channel"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-2773","authenticated-orcid":true,"given":"Ruiming","family":"Zhao","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Physiology &amp; Biophysics, School of Medicine and Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA 92697, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7404-6309","authenticated-orcid":true,"given":"Maha","family":"Nayak","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology &amp; Biophysics, School of Medicine and Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA 92697, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-4518","authenticated-orcid":true,"given":"Rong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-7815","authenticated-orcid":true,"given":"Hui","family":"Dai","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology &amp; Biophysics, School of Medicine and Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA 92697, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-3729","authenticated-orcid":true,"given":"Punyanuch","family":"Hua","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology &amp; Biophysics, School of Medicine and Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA 92697, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-2793","authenticated-orcid":true,"given":"Eduardo","family":"Perozo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-5061","authenticated-orcid":true,"given":"Steve A. N.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology &amp; Biophysics, School of Medicine and Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA 92697, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0013-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24145-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105901"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03409-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph14121303"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543780902762850"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00283"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs442"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2005.10.001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.3.2001794"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90452-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz3439"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.91.3.335"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90169-E"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413626200"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514728112"},{"key":"e_1_3_2_18_2","unstructured":"R. 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