ArticleBlood advances2019
von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Von Willebrand factor A2 domain inhibits A1-DNA binding while preserving A1-platelet interaction under flow: evidence from recombinant domain constructs.Research and practice in thrombosis and haemostasis · 2026Article
- Effect of Pulse Frequency on Shear-Induced Extension of Von Willebrand Factor in Continuous-Flow Ventricular Assist Device (CF-VAD).ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2026Article
- Vorticity-Facilitated Platelet Aggregation: a High Expansion-Ratio Stenotic Microfluidic Platform Unravels the Role of Complex Flow Dynamics in Arterial Thrombosis.Advanced healthcare materials · 2025Article
- FRET Visualization of High Mechanosensation of von Willebrand Factor to Hydrodynamic Force.Biosensors · 2025Article
- The Phenomenon of Thrombotic Microangiopathy in Cancer Patients.International journal of molecular sciences · 2024Review
- Thrombospondin-1 is an endogenous substrate of cereblon responsible for immunomodulatory drug-induced thromboembolism.Blood advances · 2024Article
- Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024Review
- The interplay between adsorption and aggregation of von Willebrand factor chains in shear flows.Biophysical journal · 2023Article
- Article
- Conformation of von Willebrand factor in shear flow revealed with stroboscopic single-molecule imaging.Blood · 2022Article
- Single-molecule imaging of von Willebrand factor reveals tension-dependent self-association.Blood · 2021Article
- Changes in Maternal Platelet Physiology during Gestation and Their Interaction with Trophoblasts.International journal of molecular sciences · 2021Review
- Complex Interaction of Platelets, von Willebrand Factor and Leukocytes, in Whole Blood at High Shear Rates Is Mediated by Platelet GPIIb/IIIa Receptor.Bulletin of experimental biology and medicine · 2021Article
- A human monoclonal antibody against the distal carboxyl terminus of ADAMTS-13 modulates its susceptibility to an inhibitor in thrombotic thrombocytopenic purpura.Journal of thrombosis and haemostasis : JTH · 2021Article
- Physical forces regulating hemostasis and thrombosis: Vessels, cells, and molecules in illustrated review.Research and practice in thrombosis and haemostasis · 2021Review
- Shear Stress-Induced Activation of von Willebrand Factor and Cardiovascular Pathology.International journal of molecular sciences · 2020Review
- Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13.Frontiers in immunology · 2020Review
- Platelet activation via dynamic conformational changes of von Willebrand factor under shear.PloS one · 2020Article
- The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model.Molecules (Basel, Switzerland) · 2019Article
- Conformation of the von Willebrand factor/factor VIII complex in quasi-static flow.The Journal of biological chemistryArticle
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
von Willebrand factor (VWF) self-association results in the homotypic binding of VWF upon exposure to fluid shear. The molecular mechanism of this process is not established. In this study, we demonstrate that the shear-dependent unfolding of the VWF A2 domain in the multimeric protein is a major regulator of protein self-association. This mechanism controls self-association on the platelet glycoprotein Ibα receptor, on collagen substrates, and during thrombus growth ex vivo. In support of this, A2-domain mutations that prevent domain unfolding due to disulfide bridging of N- and C-terminal residues ("Lock-VWF") reduce self-association and platelet activation under various experimental conditions. In contrast, reducing assay calcium concentrations, and 2 mutations that destabilize VWF-A2 conformation by preventing coordination with calcium (D1498A and R1597W VWD type 2A mutation), enhance self-association. Studies using a panel of recombinant proteins that lack the A1 domain ("ΔA1 proteins") suggest that besides pure homotypic A2 interactions, VWF-A2 may also engage other protein domains to control self-association. Addition of purified high-density lipoprotein and apolipoprotein-A1 partially blocked VWF self-association. Overall, similar conditions facilitate VWF self-association and ADAMTS13-mediated proteolysis, with low calcium and A2 disease mutations enhancing both processes, and locking-A2 blocking them simultaneously. Thus, VWF appears to have evolved 2 balancing molecular functions in a single A2 functional domain to dynamically regulate protein size in circulation: ADAMTS13-mediated proteolysis and VWF self-association. Modulating self-association rates by targeting VWF-A2 may provide novel methods to regulate the rates of thrombosis and hemostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.