Crucial role for the VWF A1 domain in binding to type IV collagen Academic Article uri icon

Overview

MeSH Major

  • Collagen Type IV
  • Mutation
  • von Willebrand Diseases
  • von Willebrand Factor

abstract

  • 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.

authors

publication date

  • April 2, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4383803

Digital Object Identifier (DOI)

  • 10.1182/blood-2014-11-610824

PubMed ID

  • 25662333

Additional Document Info

start page

  • 2297

end page

  • 304

volume

  • 125

number

  • 14