{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:55:22Z","timestamp":1771473322097,"version":"3.50.1"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"name":"van den Tol Foundation","award":["NWO\/ZonMW #902\u201326\u2013209"],"award-info":[{"award-number":["NWO\/ZonMW #902\u201326\u2013209"]}]},{"DOI":"10.13039\/501100012028","name":"Netherlands Thrombosis Foundation","doi-asserted-by":"crossref","award":["#2004.3"],"award-info":[{"award-number":["#2004.3"]}],"id":[{"id":"10.13039\/501100012028","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2006]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 vonWillebrand disease (VWD).Our objective was to test the hypothesis that the difference in phenotype is related to whether the mutated cysteine residue is involved in either interchain- or intrachain-disulfide-bond formation. The effects of three cysteine mutations which are all located in the CK-domain of VWF, C2773S (type 2A(IID)), C2739Y (type 3), and C2754W (type 3), were studied by transient expression in 293T cells. Cotransfection of wild-type (wt) and C2773S VWF constructs reproduced the plasma phenotype of heterozygous type 2A(IID) patients, with normal to high levels of VWF antigen (VWF:Ag), absence of high-molecular-weight multimers, and the presence of intervening bands between the normal multimers.In contrast, single transfections of C2739Y or C2754W resulted in a quantitativeVWF defect with lowVWF:Ag levels, and co-transfections of wt and mutant constructs resulted in a 50% reduction of VWF:Ag and only a minor effect on VWF multimerization. We demonstrated N-terminal dimerization of VWF-C2773S and both Nand C-terminal dimerization of VWF-C2754W. Our data suggest that loss of a single disulfide bond in the CK-domain ofVWF leads toa recessive, quantitativeVWF deficiency if an intrachain-disulfide bond is involved, and to a dominant-negative, qualitative defect of VWF if an interchain-disulfide bond is involved.<\/jats:p>","DOI":"10.1160\/th06-08-0460","type":"journal-article","created":{"date-parts":[[2006,12,12]],"date-time":"2006-12-12T13:22:48Z","timestamp":1165929768000},"page":"717-724","source":"Crossref","is-referenced-by-count":18,"title":["Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease"],"prefix":"10.1160","volume":"96","author":[{"given":"Pernilla","family":"Tjernberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Vos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Spaargaren-van Riel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Luken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Voorberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogier","family":"Bertina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"Eikenboom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,11,29]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH06-08-0460.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T17:10:08Z","timestamp":1588785008000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH06-08-0460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006]]},"references-count":0,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,11,29]]},"published-print":{"date-parts":[[2006]]}},"URL":"https:\/\/doi.org\/10.1160\/th06-08-0460","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006]]}}}