{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:12:02Z","timestamp":1789827122335,"version":"4.0.1"},"reference-count":54,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as destructive (Hashimoto) thyroiditis. Here we report the biophysical and structural characterization of a novel TPO construct containing only the ectodomain of TPO and lacking the propeptide. The construct was enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultracentrifugation data suggest that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that the TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional, and antigenic characteristics of TPO, an autoantigen implicated in some of the most common autoimmune diseases.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa016","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T09:23:07Z","timestamp":1580894587000},"source":"Crossref","is-referenced-by-count":18,"title":["Structural Studies of Thyroid Peroxidase Show the Monomer Interacting With Autoantibodies in Thyroid Autoimmune Disease"],"prefix":"10.1210","volume":"161","author":[{"given":"Daniel E","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah N","family":"Le","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Hoke","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G","family":"Chandler","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-663X","authenticated-orcid":false,"given":"Monika","family":"Gora","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-6724","authenticated-orcid":false,"given":"Marlena","family":"Godlewska","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Paul","family":"Banga","sequence":"first","affiliation":[{"name":"Emeritus, King\u2019s College London, London WC2R 2LS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2943-9044","authenticated-orcid":false,"given":"Ashley M","family":"Buckle","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"issue":"12","key":"2020022413593558200_CIT0001","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1055\/a-0717-5514","article-title":"Thyroid peroxidase as an autoantigen in hashimoto\u2019s disease: structure, function, and antigenicity","volume":"50","author":"Williams","year":"2018","journal-title":"Horm Metab Res."},{"key":"2020022413593558200_CIT0002","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fimmu.2017.00521","article-title":"Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases","volume":"8","author":"Fr\u00f6hlich","year":"2017","journal-title":"Front Immunol."},{"issue":"12","key":"2020022413593558200_CIT0003","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1055\/a-1057-9469","article-title":"Thyroid Peroxidase Revisited - 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