{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:50:35Z","timestamp":1790754635698,"version":"4.1.0"},"reference-count":120,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202754\/Z\/16\/Z"],"award-info":[{"award-number":["202754\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203149"],"award-info":[{"award-number":["203149"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["U105184326"],"award-info":[{"award-number":["U105184326"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["IO-0048"],"award-info":[{"award-number":["IO-0048"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["J1-7479"],"award-info":[{"award-number":["J1-7479"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P1-0048"],"award-info":[{"award-number":["P1-0048"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P1-0170"],"award-info":[{"award-number":["P1-0170"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular and Cellular Endocrinology"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.mce.2021.111309","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T02:19:16Z","timestamp":1620181156000},"page":"111309","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Cryo-EM: A new dawn in thyroid biology"],"prefix":"10.1016","volume":"531","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-303X","authenticated-orcid":false,"given":"Francesca","family":"Coscia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajda","family":"Taler-Ver\u010di\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mce.2021.111309_bib1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nature11525","article-title":"Generation of functional thyroid from embryonic stem cells","volume":"491","author":"Antonica","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.mce.2021.111309_bib2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-1-4939-6949-4_7","article-title":"Generation of functional thyroid tissue using 3D-based culture of embryonic stem cells","volume":"1597","author":"Antonica","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib3","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1016\/j.bmcl.2005.04.032","article-title":"Acyclic cyanamide-based inhibitors of cathepsin K","volume":"15","author":"Barrett","year":"2005","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.mce.2021.111309_bib4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0303-7207(80)90096-9","article-title":"The structure of newly synthesized intracellular thyroglobulin molecules","volume":"20","author":"Berg","year":"1980","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nrendo.2015.66","article-title":"Thyroid hormone transporters\u2014functions and clinical implications","volume":"11","author":"Bernal","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib6","first-page":"1918","article-title":"Multimerization of thyroglobulin (TG) during extracellular storage: isolation of highly cross-linked TG from human thyroids","volume":"81","author":"Berndorfer","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.mce.2021.111309_bib7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-4939-7902-8_8","article-title":"The deiodinase trio and thyroid hormone signaling","volume":"1801","author":"Bianco","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib8","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1172\/JCI29812","article-title":"Deiodinases: implications of the local control of thyroid hormone action","volume":"116","author":"Bianco","year":"2006","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.mce.2021.111309_bib9","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.1021\/acs.jmedchem.5b00746","article-title":"Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as potent cathepsin K inhibitors","volume":"58","author":"Bori\u0161ek","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib10","first-page":"515","article-title":"Binding, uptake, and degradation of internalized thyroglobulin in cultured thyroid and non-thyroid cells","volume":"34","author":"Botta","year":"2011","journal-title":"J. Endocrinol. Invest."},{"key":"10.1016\/j.mce.2021.111309_bib11","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1515\/bchm.2001.382.5.717","article-title":"Cysteine proteinases mediate extracellular prohormone processing in the thyroid","volume":"382","author":"Brix","year":"2001","journal-title":"Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib12","series-title":"Goiter, in: StatPearls","author":"Can","year":"2020"},{"key":"10.1016\/j.mce.2021.111309_bib13","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.99631","article-title":"Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism","volume":"3","author":"Cangul","year":"2018","journal-title":"JCI Insight"},{"key":"10.1016\/j.mce.2021.111309_bib14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.mce.2017.01.038","article-title":"Thyroid hormone biosynthesis and release","volume":"458","author":"Carvalho","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib15","first-page":"933","article-title":"Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain","volume":"130","author":"Chanoine","year":"1992","journal-title":"Endocrinology"},{"key":"10.1016\/j.mce.2021.111309_bib16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1210\/er.2009-0007","article-title":"Molecular aspects of thyroid hormone actions","volume":"31","author":"Cheng","year":"2010","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.mce.2021.111309_bib17","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1074\/jbc.RA118.001786","article-title":"Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine","volume":"293","author":"Citterio","year":"2018","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41574-019-0184-8","article-title":"The role of thyroglobulin in thyroid hormonogenesis","volume":"15","author":"Citterio","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib19","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41586-020-1995-4","article-title":"The structure of human thyroglobulin","volume":"578","author":"Coscia","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.mce.2021.111309_bib20","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1038\/s41467-020-18123-2","article-title":"Inhibitors of BRAF dimers using an allosteric site","volume":"11","author":"Cotto-Rios","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/icb\/icp053","article-title":"Evolutionary roots of iodine and thyroid hormones in cell\u2013cell signaling","volume":"49","author":"Crockford","year":"2009","journal-title":"Integr. Comp. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1172\/JCI18348","article-title":"Deubiquitination of type 2 iodothyronine deiodinase by von Hippel\u2013Lindau protein\u2013interacting deubiquitinating enzymes regulates thyroid hormone activation","volume":"112","author":"Curcio-Morelli","year":"2003","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.mce.2021.111309_bib23","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/379458a0","article-title":"Cloning and characterization of the thyroid iodide transporter","volume":"379","author":"Dai","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.mce.2021.111309_bib24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12018-011-9093-7","article-title":"Thyroid cathepsin K: roles in physiology and thyroid disease","volume":"9","author":"Dauth","year":"2011","journal-title":"Clin. Rev. Bone Miner. Metabol."},{"key":"10.1016\/j.mce.2021.111309_bib25","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1517\/14728222.2015.1018181","article-title":"Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies","volume":"19","author":"Davies","year":"2015","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.mce.2021.111309_bib26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrendo.2015.205","article-title":"Nongenomic actions of thyroid hormone","volume":"12","author":"Davis","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib27","doi-asserted-by":"crossref","first-page":"23227","DOI":"10.1074\/jbc.M000916200","article-title":"Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family","volume":"275","author":"De Deken","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib28","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1210\/en.2011-0204","article-title":"Minireview: intrinsic and extrinsic factors in thyroid gland development: an update","volume":"152","author":"De Felice","year":"2011","journal-title":"Endocrinology"},{"key":"10.1016\/j.mce.2021.111309_bib29","article-title":"Biogenic iodine and iodine-containing metabolites","volume":"1","author":"Dembitsky","year":"2006","journal-title":"Nat. Prod. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib30","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/ncb1272","article-title":"The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate","volume":"7","author":"Dentice","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.mce.2021.111309_bib31","doi-asserted-by":"crossref","first-page":"37265","DOI":"10.1074\/jbc.274.52.37265","article-title":"Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas","volume":"274","author":"Dupuy","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1124\/pr.119.018762","article-title":"Monocarboxylate transporters (SLC16): function, regulation, and role in health and disease","volume":"72","author":"Felmlee","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.mce.2021.111309_bib33","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000371741","article-title":"Iodine, thyroid autoimmunity and cancer","volume":"4","author":"Fiore","year":"2015","journal-title":"Eur. Thyroid J."},{"key":"10.1016\/j.mce.2021.111309_bib34","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1113\/jphysiol.2011.218594","article-title":"Thyroid iodide efflux: a team effort?","volume":"589","author":"Fong","year":"2011","journal-title":"J. Physiol."},{"key":"10.1016\/j.mce.2021.111309_bib35","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.1210\/jc.2010-1085","article-title":"Functional consequences of dual oxidase-thyroperoxidase interaction at the plasma membrane","volume":"95","author":"Fortunato","year":"2010","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"10.1016\/j.mce.2021.111309_bib36","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nprot.2017.004","article-title":"Advances in the field of single-particle cryo-electron microscopy over the last decade","volume":"12","author":"Frank","year":"2017","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.mce.2021.111309_bib37","doi-asserted-by":"crossref","first-page":"40128","DOI":"10.1074\/jbc.M300909200","article-title":"Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter","volume":"278","author":"Friesema","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib38","series-title":"Methimazole\u2606, in: Reference Module in Biomedical Sciences","author":"Furman","year":"2017"},{"key":"10.1016\/j.mce.2021.111309_bib39","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202050612","article-title":"Single-cell transcriptome analysis reveals thyrocyte diversity in the zebrafish thyroid gland","author":"Gillotay","year":"2020","journal-title":"EMBO Rep e50612"},{"key":"10.1016\/j.mce.2021.111309_bib40","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1096\/fj.04-2023fje","article-title":"Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site","volume":"18","author":"Gnidehou","year":"2004","journal-title":"Faseb. J."},{"key":"10.1016\/j.mce.2021.111309_bib41","doi-asserted-by":"crossref","first-page":"18269","DOI":"10.1074\/jbc.C600095200","article-title":"Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent","volume":"281","author":"Grasberger","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib42","author":"Grassi"},{"key":"10.1016\/j.mce.2021.111309_bib43","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/emboj\/18.4.793","article-title":"Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S","volume":"18","author":"Gun\u010dar","year":"1999","journal-title":"EMBO J."},{"key":"10.1016\/j.mce.2021.111309_bib44","author":"Hoffmann"},{"key":"10.1016\/j.mce.2021.111309_bib45","first-page":"5","article-title":"Evolution of ligands, receptors and metabolizing enzymes of thyroid signaling. Molecular and Cellular Endocrinology, A century of thyroid hormone research - Vol. II","volume":"459","author":"Holzer","year":"2017","journal-title":"(Int. Immunol.): Evol. Dev. Thyroid Syst."},{"key":"10.1016\/j.mce.2021.111309_bib46","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1074\/jbc.M114.605964","article-title":"A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate","volume":"290","author":"Hu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib47","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1042\/BST20170351","article-title":"Fine details in complex environments: the power of cryo-electron tomography","volume":"46","author":"Hutchings","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.mce.2021.111309_bib48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1471-2091-10-23","article-title":"Monitoring compartment-specific substrate cleavage by cathepsins B, K, L, and S at physiological pH and redox conditions","volume":"10","author":"Jordans","year":"2009","journal-title":"BMC Biochem."},{"key":"10.1016\/j.mce.2021.111309_bib49","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms16099","article-title":"Cryo-EM structure of haemoglobin at 3.2 \u00c5 determined with the Volta phase plate","volume":"8","author":"Khoshouei","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib50","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1021\/bi00436a054","article-title":"Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene","volume":"28","author":"Kimura","year":"1989","journal-title":"Biochemistry"},{"key":"10.1016\/j.mce.2021.111309_bib51","article-title":"TSH Receptor Mutations and Diseases","author":"Kleinau","year":"2000"},{"key":"10.1016\/j.mce.2021.111309_bib52","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2017.00086","article-title":"Structural\u2013functional features of the thyrotropin receptor: a class A G-protein-coupled receptor at work","volume":"8","author":"Kleinau","year":"2017","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib53","doi-asserted-by":"crossref","DOI":"10.3390\/nu12061769","article-title":"Thyroid-Gut-Axis: how does the microbiota influence thyroid function?","volume":"12","author":"Knezevic","year":"2020","journal-title":"Nutrients"},{"key":"10.1016\/j.mce.2021.111309_bib54","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.mce.2017.03.018","article-title":"Thyroid hormone transport across L-type amino acid transporters: what can molecular modelling tell us?","volume":"458","author":"Krause","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib55","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1126\/science.1251652","article-title":"The resolution revolution","volume":"343","author":"K\u00fchlbrandt","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.mce.2021.111309_bib56","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1073\/pnas.0709959105","article-title":"Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry","volume":"105","author":"K\u00fcpper","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.mce.2021.111309_bib57","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1039\/c8mt00327k","article-title":"Key aspects of the iodine metabolism in brown algae: a brief critical review","volume":"11","author":"K\u00fcpper","year":"2019","journal-title":"Metallomics"},{"key":"10.1016\/j.mce.2021.111309_bib58","doi-asserted-by":"crossref","first-page":"988","DOI":"10.3390\/md8040988","article-title":"The halogenated metabolism of Brown algae (phaeophyta), its biological importance and its environmental significance","volume":"8","author":"La Barre","year":"2010","journal-title":"Mar. Drugs"},{"key":"10.1016\/j.mce.2021.111309_bib59","doi-asserted-by":"crossref","first-page":"13541","DOI":"10.1016\/S0021-9258(18)80031-X","article-title":"Consensus sequences for early iodination and hormonogenesis in human thyroglobulin","volume":"264","author":"Lamas","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib60","doi-asserted-by":"crossref","first-page":"E1768","DOI":"10.1210\/jc.2013-2912","article-title":"Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin","volume":"98","author":"Latrofa","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.mce.2021.111309_bib61","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0142615","article-title":"Modelling of thyroid peroxidase reveals insights into its enzyme function and autoantigenicity","volume":"10","author":"Le","year":"2015","journal-title":"PloS One"},{"key":"10.1016\/j.mce.2021.111309_bib62","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41594-019-0237-7","article-title":"Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc","volume":"26","author":"Lee","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib63","doi-asserted-by":"crossref","first-page":"14858","DOI":"10.1073\/pnas.2432267100","article-title":"Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release","volume":"100","author":"Lisi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.mce.2021.111309_bib64","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41594-020-0417-5","article-title":"Allosteric regulation of mammalian Na +\/I \u2212 symporter activity by perchlorate","volume":"27","author":"Llorente-Esteban","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib65","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41574-019-0218-2","article-title":"Deiodinases and their intricate role in thyroid hormone homeostasis","volume":"15","author":"Luongo","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib66","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1089\/thy.2007.0169","article-title":"Thyroid peroxidase as an autoantigen","volume":"17","author":"McLachlan","year":"2007","journal-title":"Thyroid"},{"key":"10.1016\/j.mce.2021.111309_bib67","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1055\/s-0035-1559633","article-title":"Graves' disease mechanisms: the role of stimulating, blocking, and cleavage region TSH receptor antibodies","volume":"47","author":"Morshed","year":"2015","journal-title":"Horm. Metab. Res."},{"key":"10.1016\/j.mce.2021.111309_bib68","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.36861","article-title":"Characterisation of molecular motions in cryo-EM single-particle data by multi-body refinement in RELION","volume":"7","author":"Nakane","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.mce.2021.111309_bib69","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41586-020-2829-0","article-title":"Single-particle cryo-EM at atomic resolution","volume":"587","author":"Nakane","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.mce.2021.111309_bib70","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1126\/science.aab2413","article-title":"Exceptionally low daily energy expenditure in the bamboo-eating giant panda","volume":"349","author":"Nie","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.mce.2021.111309_bib71","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1242\/dev.145615","article-title":"Development of the thyroid gland","volume":"144","author":"Nilsson","year":"2017","journal-title":"Development"},{"key":"10.1016\/j.mce.2021.111309_bib72","article-title":"Structure and activation of the TSH receptor transmembrane domain","volume":"8","author":"N\u00fa\u00f1ez Miguel","year":"2016","journal-title":"Auto Immun. Highlights"},{"key":"10.1016\/j.mce.2021.111309_bib73","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.abb3758","article-title":"In-cell architecture of an actively transcribing-translating expressome","volume":"369","author":"O'Reilly","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.mce.2021.111309_bib74","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/j.2040-4603.2016.tb00708.x","article-title":"Hypothalamus-pituitary-thyroid Axis","volume":"6","author":"Ortiga-Carvalho","year":"2016","journal-title":"Comp. Physiol."},{"key":"10.1016\/j.mce.2021.111309_bib75","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nrendo.2014.143","article-title":"Thyroid hormone receptors and resistance to thyroid hormone disorders","volume":"10","author":"Ortiga-Carvalho","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib76","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1126\/science.2556796","article-title":"Molecular cloning of the thyrotropin receptor","volume":"246","author":"Parmentier","year":"1989","journal-title":"Science"},{"key":"10.1016\/j.mce.2021.111309_bib77","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.beem.2018.05.002","article-title":"Genetics and management of congenital hypothyroidism","volume":"32","author":"Persani","year":"2018","journal-title":"Best Pract. Res. Clin. Endocrinol. Metabol."},{"key":"10.1016\/j.mce.2021.111309_bib78","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1210\/er.2009-0040","article-title":"Thyronamines--past, present, and future","volume":"32","author":"Piehl","year":"2011","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.mce.2021.111309_bib79","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1210\/er.2012-1036","article-title":"The Na+\/I- symporter (NIS): mechanism and medical impact","volume":"35","author":"Portulano","year":"2014","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.mce.2021.111309_bib80","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1089\/thy.2007.0170","article-title":"The thyrotropin receptor in Graves' disease","volume":"17","author":"Rapoport","year":"2007","journal-title":"Thyroid"},{"key":"10.1016\/j.mce.2021.111309_bib81","article-title":"Thyroid Hormone Serum Transport Proteins","author":"Refetoff","year":"2000"},{"key":"10.1016\/j.mce.2021.111309_bib82","article-title":"Chapter 2 Thyroid Hormone Synthesis and Secretion","author":"Rousset","year":"2000"},{"key":"10.1016\/j.mce.2021.111309_bib83","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2019.00912","article-title":"Thyroid hormone hyposensitivity: from genotype to phenotype and back","volume":"10","author":"Rurale","year":"2020","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib84","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00479.2020","article-title":"A systematic review on thyroid organoid models: time-trend and its achievements","author":"Samimi","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.mce.2021.111309_bib85","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1089\/thy.2007.0034","article-title":"Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody","volume":"17","author":"Sanders","year":"2007","journal-title":"Thyroid"},{"key":"10.1016\/j.mce.2021.111309_bib86","first-page":"81","article-title":"Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody","volume":"46","author":"Sanders","year":"2011","journal-title":"J. Mol. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib87","doi-asserted-by":"crossref","first-page":"55801","DOI":"10.1074\/jbc.M410124200","article-title":"Thyroxine-thyroid hormone receptor interactions","volume":"279","author":"Sandler","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.mce.2021.111309_bib88","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41592-019-0497-5","article-title":"A cryo-FIB lift-out technique enables molecular-resolution cryo-ET within native Caenorhabditis elegans tissue","volume":"16","author":"Schaffer","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mce.2021.111309_bib89","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41592-019-0396-9","article-title":"Software tools for automated transmission electron microscopy","volume":"16","author":"Schorb","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mce.2021.111309_bib90","doi-asserted-by":"crossref","first-page":"10526","DOI":"10.1073\/pnas.1323873111","article-title":"Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism","volume":"111","author":"Schweizer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.mce.2021.111309_bib91","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1089\/thy.2013.0344","article-title":"Intrinsic regulation of thyroid function by thyroglobulin","volume":"24","author":"Sellitti","year":"2014","journal-title":"Thyroid"},{"key":"10.1016\/j.mce.2021.111309_bib92","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2018.00427","article-title":"3,5-Diiodothyronine: a novel thyroid hormone metabolite and potent modulator of energy metabolism","volume":"9","author":"Senese","year":"2018","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib93","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/MED.0000000000000188","article-title":"Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells","volume":"22","author":"Silveira","year":"2015","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"10.1016\/j.mce.2021.111309_bib94","doi-asserted-by":"crossref","DOI":"10.1021\/ja053564h","article-title":"Comparisons of NMR spectral quality and success in crystallization demonstrate that NMR and X-ray crystallography are complementary methods for small protein structure determination","volume":"127","author":"Snyder","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.mce.2021.111309_bib95","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.bbrc.2012.03.046","article-title":"Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum","volume":"420","author":"Sue","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib96","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/s41594-020-0501-x","article-title":"Structures of mouse DUOX1\u2013DUOXA1 provide mechanistic insights into enzyme activation and regulation","volume":"27","author":"Sun","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.mce.2021.111309_bib97","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2018.00765","article-title":"Antigenic \u201chot- spots\u201d on the TSH receptor hinge region","volume":"9","author":"Sun","year":"2019","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib98","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1530\/JOE-10-0486","article-title":"Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth","volume":"209","author":"Suzuki","year":"2011","journal-title":"J. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib99","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0300-9084(99)80110-2","article-title":"Molecular evolution of thyroid peroxidase","volume":"81","author":"Taurog","year":"1999","journal-title":"Biochimie"},{"key":"10.1016\/j.mce.2021.111309_bib100","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrendo.2018.18","article-title":"Global epidemiology of hyperthyroidism and hypothyroidism","volume":"14","author":"Taylor","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib101","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/78630","article-title":"The mammary gland iodide transporter is expressed during lactation and in breast cancer","volume":"6","author":"Tazebay","year":"2000","journal-title":"Nat. Med."},{"key":"10.1016\/j.mce.2021.111309_bib102","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1089\/thy.2019.0034","article-title":"Dimerization of the sodium\/iodide symporter","volume":"29","author":"Thompson","year":"2019","journal-title":"Thyroid"},{"key":"10.1016\/j.mce.2021.111309_bib103","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1210\/en.2005-1149","article-title":"The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland","volume":"147","author":"van den Hove","year":"2006","journal-title":"Endocrinology"},{"key":"10.1016\/j.mce.2021.111309_bib104","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0303-7207(85)90162-5","article-title":"Structure, expression and regulation of the thyroglobulin gene","volume":"40","author":"Vassart","year":"1985","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib105","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1210\/endo.132.1.8380383","article-title":"Molecular basis of the thyroglobulin synthesis defect in Dutch goats","volume":"132","author":"Veenboer","year":"1993","journal-title":"Endocrinology"},{"key":"10.1016\/j.mce.2021.111309_bib106","author":"Venturi"},{"key":"10.1016\/j.mce.2021.111309_bib107","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3390\/ijms22010462","article-title":"The thyroid hormone transporter Mct8 restricts cathepsin-mediated thyroglobulin processing in male mice through thyroid auto-regulatory mechanisms that encompass autophagy","volume":"22","author":"Venugopalan","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.mce.2021.111309_bib108","article-title":"Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.mce.2021.111309_bib109","first-page":"261","article-title":"Genetic defects of hydrogen peroxide generation in the thyroid gland","volume":"36","author":"Weber","year":"2013","journal-title":"J. Endocrinol. Invest."},{"key":"10.1016\/j.mce.2021.111309_bib110","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1055\/a-0717-5514","article-title":"Thyroid peroxidase as an autoantigen in hashimoto's disease: structure, function, and antigenicity","volume":"50","author":"Williams","year":"2018","journal-title":"Horm. Metab. Res."},{"key":"10.1016\/j.mce.2021.111309_bib111","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ando.2011.03.006","article-title":"Extrathyroidal expression of TSH receptor","volume":"72","author":"Williams","year":"2011","journal-title":"Ann. Endocrinol."},{"key":"10.1016\/j.mce.2021.111309_bib112","doi-asserted-by":"crossref","DOI":"10.1074\/mcp.RA120.002168","article-title":"Thyroglobulin interactome profiling defines altered proteostasis topology associated with thyroid dyshormonogenesis","author":"Wright","year":"2021","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.mce.2021.111309_bib113","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41467-020-20466-9","article-title":"Structures of human dual oxidase 1 complex in low-calcium and high-calcium states","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib114","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1043-2760(00)00263-0","article-title":"Gene regulation by thyroid hormone","volume":"11","author":"Wu","year":"2000","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.mce.2021.111309_bib115","doi-asserted-by":"crossref","DOI":"10.1021\/ja053565+","article-title":"NMR and X-ray crystallography, complementary tools in structural proteomics of small proteins","volume":"127","author":"Yee","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.mce.2021.111309_bib116","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1128\/MCB.01498-08","article-title":"The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase","volume":"29","author":"Zavacki","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.mce.2021.111309_bib117","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1038\/s41467-020-16334-1","article-title":"Cooperative transport mechanism of human monocarboxylate transporter 2","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mce.2021.111309_bib118","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1021\/acs.jcim.9b01114","article-title":"Mapping of ion and substrate binding sites in human sodium iodide symporter (hNIS)","volume":"60","author":"Zhekova","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.mce.2021.111309_bib119","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.42166","article-title":"New tools for automated high-resolution cryo-EM structure determination in RELION-3","volume":"7","author":"Zivanov","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.mce.2021.111309_bib120","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s12020-019-02018-4","article-title":"Novel thyroid hormones","volume":"66","author":"Zucchi","year":"2019","journal-title":"Endocrine"}],"container-title":["Molecular and Cellular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0303720721001532?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0303720721001532?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:16:29Z","timestamp":1759587389000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0303720721001532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":120,"alternative-id":["S0303720721001532"],"URL":"https:\/\/doi.org\/10.1016\/j.mce.2021.111309","relation":{},"ISSN":["0303-7207"],"issn-type":[{"value":"0303-7207","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cryo-EM: A new dawn in thyroid biology","name":"articletitle","label":"Article Title"},{"value":"Molecular and Cellular Endocrinology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mce.2021.111309","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 MRC Laboratory of Molecular Biology. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"111309"}}