{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:42:44Z","timestamp":1779284564969,"version":"3.51.4"},"reference-count":9,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,7,14]]},"abstract":"<jats:p>\n            Moseng\n            <jats:italic>et al.<\/jats:italic>\n            recently reported four cryo\u2013electron microscopy structures of the human Na-K-2Cl cotransporter-1 (hNKCC1), both in the absence and presence of bound loop diuretic (furosemide or bumetanide). This research article included high-resolution structural information for a previously undefined structure of apo-hNKCC1 containing both the transmembrane and cytosolic carboxyl-terminal domains. The manuscript also demonstrated various conformational states of this cotransporter induced by diuretic drugs. On the basis of the structural information, the authors proposed a scissor-like inhibition mechanism that involves a coupled movement between the cytosolic and transmembrane domains of hNKCC1. This work has provided important insights into the mechanism of inhibition and substantiated the concept of a long-distance coupling involving movements of both the transmembrane and carboxyl-terminal cytoplasmic domains for inhibition.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adi5716","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T17:58:38Z","timestamp":1689184718000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Response to Comment on \u201cInhibition mechanism of NKCC1 involves the carboxyl terminus and long-range conformational coupling\u201d"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-7283","authenticated-orcid":true,"given":"Mitchell A.","family":"Moseng","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3646-327X","authenticated-orcid":true,"given":"Chih-Chia","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-0145","authenticated-orcid":true,"given":"Philip A.","family":"Klenotic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3702-1599","authenticated-orcid":true,"given":"Eric","family":"Delpire","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-1227","authenticated-orcid":true,"given":"Edward W.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq0952"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2052252518018304"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021110169"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1438-2"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0731-1"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107294"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4169"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01021-2"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.309211"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adi5716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:00:34Z","timestamp":1704841234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adi5716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,14]]},"references-count":9,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2023,7,14]]}},"alternative-id":["10.1126\/sciadv.adi5716"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adi5716","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,14]]},"assertion":[{"value":"2023-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi5716"}}