{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:03:26Z","timestamp":1790705006255,"version":"4.1.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to obtain homogeneous preparations of recombinant TPO for structural studies, we investigated the role of the large propeptide sequence in TPO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>An engineered recombinant human TPO preparation expressed in Chinese hamster ovary (CHO) cells lacking the propeptide (TPO\u0394pro; amino acid residues 21\u2013108) was characterized and its properties compared to wild-type TPO. Plasma membrane localization was determined by cell surface protein biotinylation, and biochemical studies were performed to evaluate enzymatic activity and the effect of deglycosylation. Immunological investigations using autoantibodies from AITD patients and other epitope-specific antibodies that recognize conformational determinants on TPO were evaluated for binding to TPO\u0394pro by flow cytometry, immunocytochemistry, and capture enzyme-linked immunosorbent assay. Molecular modeling and dynamics simulation of TPO\u0394pro comprising a dimer of myeloperoxidase-like domains was performed in order to investigate the impact of propeptide removal and the role of glycosylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The TPO\u0394pro was expressed on the cell surface at comparable levels to wild-type TPO. The TPO\u0394pro was enzymatically active and recognized by patients' autoantibodies and a panel of epitope-specific antibodies, confirming structural integrity of the two major conformational determinants recognized by autoantibodies. Faithful intracellular trafficking and N-glycosylation of TPO\u0394pro was also maintained. Molecular modeling and dynamics simulations were consistent with these observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our results point to a redundant role for the propeptide sequence in TPO. The successful expression of TPO\u0394pro in a membrane-anchored, enzymatically active form that is insensitive to intramolecular proteolysis, and importantly is recognized by patients' autoantibodies, is a key advance for purification of substantial quantities of homogeneous preparation of TPO for crystallization, structural, and immunological studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0127","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T14:19:10Z","timestamp":1368454750000},"page":"371-382","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":31,"title":["A Redundant Role of Human Thyroid Peroxidase Propeptide for Cellular, Enzymatic, and Immunological Activity"],"prefix":"10.1177","volume":"24","author":[{"given":"Marlena","family":"Godlewska","sequence":"first","affiliation":[{"name":"Medical Center of Postgraduate Education","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"G\u00f3ra","sequence":"additional","affiliation":[{"name":"Polish Academy of Sciences","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M.","family":"Buckle","sequence":"additional","affiliation":[{"name":"Monash University","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin T.","family":"Porebski","sequence":"additional","affiliation":[{"name":"Monash University","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Helen","family":"Kemp","sequence":"additional","affiliation":[{"name":"University of Sheffield","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Sutton","sequence":"additional","affiliation":[{"name":"King's College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Czarnocka","sequence":"additional","affiliation":[{"name":"Medical Center of Postgraduate Education","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Paul","family":"Banga","sequence":"additional","affiliation":[{"name":"King's College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,2,1]]},"reference":[{"key":"e_1_3_3_2_2","first-page":"48","volume-title":"Werner and Ingbar's the Thyroid: A Fundamental and Clinical Text","author":"Kopp P","year":"2012","unstructured":"Kopp P. 2012. Thyroid hormone synthesis In: Braverman LE, , Cooper D (eds) Werner and Ingbar's the Thyroid: A Fundamental and Clinical Text. Tenth edition. Lippincott Williams & Wilkins, Philadelphia, pp 48\u201374."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00060793-199811000-00007"},{"key":"e_1_3_3_4_2","first-page":"110","volume-title":"The Thyroid and Autoimmunity","author":"Gora M","year":"2006","unstructured":"Gora M, , Dubska M, , Jastrzebska-Bohaterewicz E, , Gardas A. 2006. Profile of autoantibodies to the two immunodominant regions of thyroid peroxidase in autoimmunity. In: Wiersinga WM, , Drexhage HA, , Weetman AP, , Butz S (eds) The Thyroid and Autoimmunity. Georg Thieme Verlag, New York, pp 110\u2013117."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0169"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-3-1211"},{"key":"e_1_3_3_7_2","first-page":"2639","article-title":"Immunoglobulin G kappa antithyroid peroxidase antibodies in Hashimoto's thyroiditis: epitope-mapping analysis","volume":"82","author":"Czarnocka B","year":"1997","unstructured":"Czarnocka B, , Janota-Bzowski M, , McIntosh RS, , Asghar MS, , Watson PF, , Kemp EH, , Carayon P, , Weetman AP. 1997. Immunoglobulin G kappa antithyroid peroxidase antibodies in Hashimoto's thyroiditis: epitope-mapping analysis. 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