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Home / Equine Research Bank / J Thromb Haemost / von Willebrand factor A1 domain can adequately substitute fo...
Journal of thrombosis and haemostasis : JTH2006; 4(10); 2151-2161; doi: 10.1111/j.1538-7836.2006.02111.x

von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen.

Abstract: Binding of von Willebrand factor (VWF) to platelet GPIbalpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objective: Using VWF, VWF lacking A1 (DeltaA1-VWF) or A3 (DeltaA3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residues 1262-1492) or A3 (residues 1671-1878), fused to glutathione-S-transferase (GST-A1 and GST-A3), we have re-investigated the role of A1 in platelet recruitment to surfaces of collagen. Results: In flow, measurable binding of DeltaA3-VWF occurred to horse tendon, but also to human type III collagen. GST-A1 and GST-A3 both competed for binding of DeltaA1-VWF and DeltaA3-VWF to horse tendon collagen fibrils in static conditions and to human collagen III during plasmon surface resonance studies, substantiating overlapping binding sites on both collagens for A1 and A3. Heparin did not affect A3-mediated binding of VWF and DeltaA1-VWF, but inhibited binding to horse tendon collagen of GST-A1 and DeltaA3-VWF. Furthermore, A1-mediated binding to type III collagen of DeltaA3-VWF binding was strongly salt-sensitive. During perfusions at wall shear rate 2500 s(-1) of calcein-labeled platelets in reconstituted blood, DeltaA3-VWF and H1786A-VWF triggered platelet binding to horse tendon collagen comparably and as potently as VWF, and to human type III collagen, only fivefold less potently, DeltaA1-VWF being inactive. Additional flow-controlled interaction studies with DeltaA3-VWF, H1786A-VWF, the collagen-VWF antagonist saratin, heparin and the VWF neutralizing antibody 82D6A3 confirmed that H1786A-VWF binds to collagen exclusively via A1. Conclusions: Hence, in shear forces the VWF A1 domain can assume the role of A3 to trigger substantial platelet recruitment to human collagen fibres.
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Publication Date: 2006-06-29 PubMed ID: 16805860DOI: 10.1111/j.1538-7836.2006.02111.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how the von Willebrand factor (VWF) protein’s A1 domain can effectively replace the A3 domain in attracting circulating platelets to collagen, which is instrumental in blood clotting.

Research Methods

  • The scientists utilized various versions of VWF for the study: the normal form, a form lacking the A1 domain (DeltaA1-VWF), a form lacking the A3 domain (DeltaA3-VWF), and a form with a defective A3 domain (H1786A-VWF).
  • These were combined with custom-made A1 and A3 domains fused to the protein glutathione-S-transferase (GST-A1 and GST-A3).
  • The role of the A1 domain in attracting platelets to collagen surfaces was reexamined through these combinations.

Findings

  • In a flowing environment, DeltaA3-VWF showed observable binding to horse tendon collagen and human type III collagen.
  • In static conditions, both GST-A1 and GST-A3 competed for binding with DeltaA1-VWF and DeltaA3-VWF to collagen fibrils from horse tendons.
  • This competition also took place on human collagen III during surface plasmon resonance studies, suggesting the A1 and A3 domains have overlapping binding sites on both types of collagen.
  • The presence of a blood thinner, heparin, did not affect A3-mediated binding of VWF and DeltaA1-VWF but did inhibit GST-A1 and DeltaA3-VWF’s binding to horse tendon collagen.
  • A1-mediated binding of DeltaA3-VWF to type III collagen was greatly influenced by salt.

Conclusions

  • During perfusions, DeltaA3-VWF and H1786A-VWF triggered platelets to bind to collagen just as effectively as the normal VWF would.
  • However, a form lacking the A1 domain (DeltaA1-VWF) was inactive in the same conditions.
  • In cases of high shear forces, the A1 domain of the VWF protein can replace the A3 domain to trigger significant platelet binding to collagen fibres, pivotal in blood clotting.

This study provides significant insights into the role of different domains of VWF in triggering platelet binding to collagen fibres during blood clotting.

Cite This Article

APA
Bonnefoy A, Romijn RA, Vandervoort PA, VAN Rompaey I, Vermylen J, Hoylaerts MF. (2006). von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen. J Thromb Haemost, 4(10), 2151-2161. https://doi.org/10.1111/j.1538-7836.2006.02111.x

Publication

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7933
NlmUniqueID: 101170508
Country: England
Language: English
Volume: 4
Issue: 10
Pages: 2151-2161

Researcher Affiliations

Bonnefoy, A
  • Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Romijn, R A
    Vandervoort, P A H
      VAN Rompaey, I
        Vermylen, J
          Hoylaerts, M F

            MeSH Terms

            • Animals
            • Binding Sites
            • Blood Platelets / metabolism
            • Collagen / chemistry
            • Dose-Response Relationship, Drug
            • Glutathione Transferase / metabolism
            • Horses
            • Humans
            • Platelet Adhesiveness
            • Protein Binding
            • Protein Structure, Tertiary
            • Recombinant Proteins / chemistry
            • Salivary Proteins and Peptides / chemistry
            • Stress, Mechanical
            • Surface Plasmon Resonance
            • Time Factors
            • von Willebrand Factor / chemistry
            • von Willebrand Factor / genetics
            • von Willebrand Factor / physiology

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