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The terminal Cys288\/Cys326 disulfide bond at domain V has been associated with different cysteine redox states. The role of this disulfide bond in conformational dynamics of this protein has not been investigated so far. Here, we report on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine; TCEP) of \u03b22GPI. Specific reduction was demonstrated by Western blot and mass spectrometry analyses confirming majority targeting to the fifth domain of \u03b22GPI. Atomic force microscopy images suggested that reduced \u03b22GPI shows a slightly higher proportion of open conformation and is more flexible compared to the untreated protein as confirmed by modelling studies. We have determined a strong increase in the binding of pathogenic APS autoantibodies to reduced \u03b22GPI as demonstrated by ELISA. Our study is relevant for understanding the effect of \u03b22GPI reduction on the protein structure and its implications for antibody binding in APS patients.<\/jats:p>","DOI":"10.1038\/s41598-021-84021-2","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T11:04:11Z","timestamp":1614251051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Specific domain V reduction of beta-2-glycoprotein I induces protein flexibility and alters pathogenic antibody binding"],"prefix":"10.1038","volume":"11","author":[{"given":"Ina","family":"Buchholz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nestler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarat","family":"Tharad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kulke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Radziszewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera M.","family":"Ripoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Hammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Toca-Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Delcea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"84021_CR1","doi-asserted-by":"publisher","first-page":"6228","DOI":"10.1093\/emboj\/18.22.6228","volume":"18","author":"R Schwarzenbacher","year":"1999","unstructured":"Schwarzenbacher, R. et al. 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