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Crucial role for the VWF A1 domain in binding to type IV collagen
Journal article   Open access   Peer reviewed

Crucial role for the VWF A1 domain in binding to type IV collagen

Veronica H Flood, Abraham C Schlauderaff, Sandra L Haberichter, Tricia L Slobodianuk, Paula M Jacobi, Daniel B Bellissimo, Pamela A Christopherson, Kenneth D Friedman, Joan Cox Gill, Raymond G Hoffmann, …
Blood, v 125(14), pp 2297-2304
02 Apr 2015
DOI: https://doi.org/10.1182/blood-2014-11-610824
PMID: 25662333
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1182/blood-2014-11-610824View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Binding Sites Case-Control Studies Cells, Cultured Collagen Type IV - metabolism Flow Cytometry Humans Mice Mutagenesis, Site-Directed Mutation - genetics Protein Binding Protein Conformation Protein Structure, Tertiary Structure-Activity Relationship von Willebrand Diseases - genetics von Willebrand Diseases - metabolism von Willebrand Factor - chemistry von Willebrand Factor - genetics von Willebrand Factor - metabolism
Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed. We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain. We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis.

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Collaboration types
Domestic collaboration
Web of Science research areas
Hematology
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