Peter J Lenting, Cécile V Denis, Olivier D Christophe
{"title":"How unique structural adaptations support and coordinate the complex function of von Willebrand factor.","authors":"Peter J Lenting, Cécile V Denis, Olivier D Christophe","doi":"10.1182/blood.2023023277","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>von Willebrand factor (VWF) is a multimeric protein consisting of covalently linked monomers, which share an identical domain architecture. Although involved in processes such as inflammation, angiogenesis, and cancer metastasis, VWF is mostly known for its role in hemostasis, by acting as a chaperone protein for coagulation factor VIII (FVIII) and by contributing to the recruitment of platelets during thrombus formation. To serve its role in hemostasis, VWF needs to bind a variety of ligands, including FVIII, platelet-receptor glycoprotein Ib-α, VWF-cleaving protease ADAMTS13, subendothelial collagen, and integrin α-IIb/β-3. Importantly, interactions are differently regulated for each of these ligands. How are these binding events accomplished and coordinated? The basic structures of the domains that constitute the VWF protein are found in hundreds of other proteins of prokaryotic and eukaryotic organisms. However, the determination of the 3-dimensional structures of these domains within the VWF context and especially in complex with its ligands reveals that exclusive, VWF-specific structural adaptations have been incorporated in its domains. They provide an explanation of how VWF binds its ligands in a synchronized and timely fashion. In this review, we have focused on the domains that interact with the main ligands of VWF and discuss how elucidating the 3-dimensional structures of these domains has contributed to our understanding of how VWF function is controlled. We further detail how mutations in these domains that are associated with von Willebrand disease modulate the interaction between VWF and its ligands.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2174-2184"},"PeriodicalIF":21.0000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/blood.2023023277","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: von Willebrand factor (VWF) is a multimeric protein consisting of covalently linked monomers, which share an identical domain architecture. Although involved in processes such as inflammation, angiogenesis, and cancer metastasis, VWF is mostly known for its role in hemostasis, by acting as a chaperone protein for coagulation factor VIII (FVIII) and by contributing to the recruitment of platelets during thrombus formation. To serve its role in hemostasis, VWF needs to bind a variety of ligands, including FVIII, platelet-receptor glycoprotein Ib-α, VWF-cleaving protease ADAMTS13, subendothelial collagen, and integrin α-IIb/β-3. Importantly, interactions are differently regulated for each of these ligands. How are these binding events accomplished and coordinated? The basic structures of the domains that constitute the VWF protein are found in hundreds of other proteins of prokaryotic and eukaryotic organisms. However, the determination of the 3-dimensional structures of these domains within the VWF context and especially in complex with its ligands reveals that exclusive, VWF-specific structural adaptations have been incorporated in its domains. They provide an explanation of how VWF binds its ligands in a synchronized and timely fashion. In this review, we have focused on the domains that interact with the main ligands of VWF and discuss how elucidating the 3-dimensional structures of these domains has contributed to our understanding of how VWF function is controlled. We further detail how mutations in these domains that are associated with von Willebrand disease modulate the interaction between VWF and its ligands.
期刊介绍:
Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.