{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:14:32Z","timestamp":1785870872303,"version":"3.56.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"07","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The platelet receptor glycoprotein (GP) IIb\/IIIa, formed by integrins \u03b1IIb and \u03b23, plays an important role in platelet adhesion and aggregation. Its major binding site is the arginine-glycine-aspartic acid (RGD) sequence present in several adhesive proteins. Upon platelet activation, inside-out signaling activates the complex permitting binding to RGD motif containing proteins, such as von Willebrand factor (VWF). VWF is a large multidomain plasma GP essential to primary hemostasis, which can directly interact with platelets because it exhibits binding sites for GPIb\u03b1 and GPIIb\/IIIa in its A1 and C4 domain, respectively. A vast variety of VWF variants have been identified in which domain-specific mutations affect distinct functions of VWF but reduced GPIIb\/IIIa binding has barely been studied so far. Here, we strived to investigate the influence of C domain mutations, which have been identified in patients diagnosed with von Willebrand disease (VWD), on VWF\u2013GPIIb\/IIIa interaction. To determine binding to membrane-incorporated GPIIb\/IIIa in the absence of GPIb\u03b1, we developed and validated a cell-based binding assay which uses HEK293 cells stably expressing a constitutively active form of the GPIIb\/IIIa receptor complex on their plasma membrane. By employing this assay, we measured GPIIb\/IIIa binding of 14 VWF C domain mutants identified in VWD patients. Mutants p.Cys2257Arg, p.Gly2441Cys, p.Cys2477Tyr, and p.Pro2722Ala exhibited significantly reduced binding. Summarizing, we have developed a useful research tool to specifically investigate GPIIb\/IIIa interaction with its protein binding partners and identified four VWF variants that exhibit impaired GPIIb\/IIIa binding. At least in the homozygous state, this defect could contribute to the VWD phenotype.<\/jats:p>","DOI":"10.1055\/s-0039-1687878","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T23:00:10Z","timestamp":1556578810000},"page":"1102-1111","source":"Crossref","is-referenced-by-count":11,"title":["Alteration in GPIIb\/IIIa Binding of VWD-Associated von Willebrand Factor Variants with C-Terminal Missense Mutations"],"prefix":"10.1055","volume":"119","author":[{"given":"Gesa","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Obser","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Marggraf","sequence":"additional","affiliation":[{"name":"Center for Anesthesiology and Intensive Care Medicine, Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Schneppenheim","sequence":"additional","affiliation":[{"name":"Medilys Central Laboratory Coagulation, Asklepios Clinic Altona, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Budde","sequence":"additional","affiliation":[{"name":"Medilys Central Laboratory Coagulation, Asklepios Clinic Altona, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Schneppenheim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Brehm","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2019,4,29]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0039-1687878.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T01:59:16Z","timestamp":1561427956000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0039-1687878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,29]]},"references-count":0,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2019,6,24]]},"published-print":{"date-parts":[[2019,7]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0039-1687878","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,29]]}}}