{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:09:53Z","timestamp":1791346193531,"version":"4.3.1"},"reference-count":83,"publisher":"National Academy of Sciences","issue":"37","license":[{"start":{"date-parts":[[2017,2,25]],"date-time":"2017-02-25T00:00:00Z","timestamp":1487980800000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK-41544"],"award-info":[{"award-number":["DK-41544"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM-114250"],"award-info":[{"award-number":["GM-114250"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,9,13]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The Na\n                    <jats:sup>+<\/jats:sup>\n                    \/I\n                    <jats:sup>\u2212<\/jats:sup>\n                    symporter (NIS) uses the Na\n                    <jats:sup>+<\/jats:sup>\n                    electrochemical gradient to actively transport I\n                    <jats:sup>\u2212<\/jats:sup>\n                    into the thyroid with a 2 Na\n                    <jats:sup>+<\/jats:sup>\n                    :1 I\n                    <jats:sup>\u2212<\/jats:sup>\n                    stoichiometry. In NIS and related transporters, one of the two Na\n                    <jats:sup>+<\/jats:sup>\n                    binding sites, Na2, includes a Ser and a Thr residue. We determined that, besides these residues, four other amino acids participate in binding Na\n                    <jats:sup>+<\/jats:sup>\n                    at the Na2 site, at different stages of the transport cycle. These residues are conserved throughout the entirety of solute carrier family 5 (SLC5), to which NIS belongs. Replacing any of these residues has a marked effect on transport and on the dynamics of NIS. These results not only deepen our understanding of the mechanism of transport by NIS but are also relevant to the study of other Na\n                    <jats:sup>+<\/jats:sup>\n                    -driven cotransporters.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1607231113","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T22:28:44Z","timestamp":1472164124000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Na\n                    <sup>+<\/sup>\n                    coordination at the Na2 site of the Na\n                    <sup>+<\/sup>\n                    \/I\n                    <sup>\u2212<\/sup>\n                    symporter"],"prefix":"10.1073","volume":"113","author":[{"given":"Giuseppe","family":"Ferrandino","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Nicola","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuly E.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacia","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Mario","family":"Amzel","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(93)90017-I"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/379458a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1083"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.43.27230"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1108278108"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707207104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/78630"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/026010600902000204"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-7-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00509.2008"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.241307"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4948"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1036"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5568"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22657"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-229138"},{"key":"e_1_3_3_17_2","first-page":"3305","article-title":"The iodide-transport-defect-causing mutation R124H: A \u03b4-amino group at position 124 is critical for maturation and trafficking of the Na+\/I\u2212 symporter","volume":"126","author":"Paroder V","year":"2013","unstructured":"V Paroder, JP Nicola, CS Ginter, N Carrasco, The iodide-transport-defect-causing mutation R124H: A \u03b4-amino group at position 124 is critical for maturation and trafficking of the Na+\/I\u2212 symporter. J Cell Sci 126, 3305\u20133313 (2013).","journal-title":"J Cell Sci"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160406"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404936101"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2548"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01904-1"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0071"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00522-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00898"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0162"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1824"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-122a"},{"key":"e_1_3_3_28_2","first-page":"2940","article-title":"Recurrent T354P mutation of the Na+\/I\u2212 symporter in patients with iodide transport defect","volume":"83","author":"Fujiwara H","year":"1998","unstructured":"H Fujiwara, , Recurrent T354P mutation of the Na+\/I\u2212 symporter in patients with iodide transport defect. J Clin Endocrinol Metab 83, 2940\u20132943 (1998).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2000.10.471"},{"key":"e_1_3_3_30_2","first-page":"3248","article-title":"A novel mutation in the sodium\/iodide symporter gene in the largest family with iodide transport defect","volume":"84","author":"Kosugi S","year":"1999","unstructured":"S Kosugi, S Bhayana, HJ Dean, A novel mutation in the sodium\/iodide symporter gene in the largest family with iodide transport defect. J Clin Endocrinol Metab 84, 3248\u20133253 (1999).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_31_2","first-page":"3373","article-title":"Novel, missense and loss-of-function mutations in the sodium\/iodide symporter gene causing iodide transport defect in three Japanese patients","volume":"83","author":"Kosugi S","year":"1998","unstructured":"S Kosugi, S Inoue, A Matsuda, SM Jhiang, Novel, missense and loss-of-function mutations in the sodium\/iodide symporter gene causing iodide transport defect in three Japanese patients. J Clin Endocrinol Metab 83, 3373\u20133376 (1998).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.8.8767"},{"key":"e_1_3_3_33_2","first-page":"4123","article-title":"High prevalence of T354P sodium\/iodide symporter gene mutation in Japanese patients with iodide transport defect who have heterogeneous clinical pictures","volume":"83","author":"Kosugi S","year":"1998","unstructured":"S Kosugi, , High prevalence of T354P sodium\/iodide symporter gene mutation in Japanese patients with iodide transport defect who have heterogeneous clinical pictures. J Clin Endocrinol Metab 83, 4123\u20134129 (1998).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_34_2","first-page":"3966","article-title":"A homozygous missense mutation of the sodium\/iodide symporter gene causing iodide transport defect","volume":"82","author":"Matsuda A","year":"1997","unstructured":"A Matsuda, S Kosugi, A homozygous missense mutation of the sodium\/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab 82, 3966\u20133971 (1997).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7594"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1504"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700147200"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0027"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03978"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2894"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164440"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07819"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209039109"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08143"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.038422"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319218110"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00446.2011"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602319200"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.617555"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.07.044"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511365"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21287"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9720641"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706741200"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10737"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00397.2011"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/10\/5\/056004"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.11.004"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00276625"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.09.005"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1039\/b927492h"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005521200"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvr062"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308253200"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111008200"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-206110"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-168"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-177-2_10"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)74712-2"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10321"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10272"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4655(95)00042-E"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000880"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00935"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2006.07.002"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)76033-X"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0278(97)00024-2"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.77.1905"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13365"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525378113"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1607231113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1607231113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:37:48Z","timestamp":1649813868000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1607231113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,25]]},"references-count":83,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2016,9,13]]}},"alternative-id":["10.1073\/pnas.1607231113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1607231113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,25]]},"assertion":[{"value":"2016-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}