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Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T\n                    <jats:sub>3<\/jats:sub>\n                    ) and thyroxine (T\n                    <jats:sub>4<\/jats:sub>\n                    ) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2\u2009\u00c5 resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography\u2013mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-27693-8","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T06:02:59Z","timestamp":1641794579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Cryo-EM structure of native human thyroglobulin"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8311-9231","authenticated-orcid":false,"given":"Ricardo","family":"Adaixo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo D.","family":"Righetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3149-2381","authenticated-orcid":false,"given":"Alexander","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-4592","authenticated-orcid":false,"given":"Henning","family":"Stahlberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-4921","authenticated-orcid":false,"given":"Nicholas M. 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