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Fibronectin binding to von Willebrand factor occurs via the A1 domain
Author(s) -
Keesler Daniel A.,
Slobodianuk Tricia L.,
Kochelek Caroline E.,
Skaer Chad W.,
Haberichter Sandra L.,
Flood Veronica H.
Publication year - 2021
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12534
Subject(s) - fibronectin , von willebrand factor , extracellular matrix , chemistry , recombinant dna , fibronectins , microbiology and biotechnology , platelet , biochemistry , biology , immunology , gene
Background Collagen interactions with von Willebrand factor (VWF) perform an important role in initiation of hemostasis. Objectives We hypothesized that in addition to collagen, other extracellular matrix (ECM) proteins such as fibronectin can bind VWF. Methods Fibronectin‐VWF interactions were measured by ELISA using both plasma‐derived and recombinant VWF–containing variants in specific domains. Inhibition was measured by antibody competition using antibodies directed against both VWF and fibronectin. Binding affinities were measured by the Octet Biosensor for fibronectin and collagen IV. Results Fibronectin was able to bind both plasma‐derived and recombinant wild‐type VWF. This interaction was inhibited by both anti‐VWF antibodies and collagen types III and IV. Several VWF A1 domain variants in the region of the collagen IV binding site also demonstrated absent fibronectin binding, as did variants with defects in high‐molecular‐weight multimers. Binding affinity testing showed fibronectin has a strong affinity for VWF, in a range similar to that of collagen IV. Fibronectin binds VWF via a restricted region of the A1 domain. This interaction requires high‐molecular‐weight multimers and is similar to that seen with vascular collagens. Conclusions Therefore, VWF would appear to be the common factor linking platelet adhesion to various ECM proteins and facilitating hemostasis under conditions of ECM exposure.

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