ArticleProceedings of the National Academy of Sciences of the United States of America2015
Force-induced on-rate switching and modulation by mutations in gain-of-function von Willebrand diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.Blood · 2024Article
- Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024Review
- Autoinhibitory module underlies species difference in shear activation of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2022Article
- Von Willebrand factor A1 domain stability and affinity for GPIbα are differentially regulated by itseLife · 2022Article
- Engineered Molecular Therapeutics Targeting Fibrin and the Coagulation System: a Biophysical Perspective.Biophysical reviews · 2022Review
- Nano-Precision Tweezers for Mechanosensitive Proteins and Beyond.Molecules and cells · 2022Review
- Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.Nature communications · 2021Article
- Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF.BMC molecular and cell biology · 2020Article
- Platelet-type von Willebrand disease: Local disorder of the platelet GPIbα β-switch drives high-affinity binding to von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2019Article
- Force-Regulated Refolding of the Mechanosensory Domain in the Platelet Glycoprotein Ib-IX Complex.Biophysical journal · 2019Article
- Electrostatic Steering Enables Flow-Activated Von Willebrand Factor to Bind Platelet Glycoprotein, Revealed by Single-Molecule Stretching and Imaging.Journal of molecular biology · 2019Article
- In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow.Biophysical journal · 2019Article
- A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2017Article
- Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.Nature communications · 2017Article
- Enhanced Local Disorder in a Clinically Elusive von Willebrand Factor Provokes High-Affinity Platelet Clumping.Journal of molecular biology · 2017Article
- Probing the structural dynamics of proteins and nucleic acids with optical tweezers.Current opinion in structural biology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the ultralong vascular protein von Willebrand factor (VWF) cause the common human bleeding disorder, von Willebrand disease (VWD). The A1 domain in VWF binds to glycoprotein Ibα (GPIbα) on platelets, in a reaction triggered, in part, by alterations in flow during bleeding. Gain-of-function mutations in A1 and GPIbα in VWD suggest conformational regulation. We report that force application switches A1 and/or GPIbα to a second state with faster on-rate, providing a mechanism for activating VWF binding to platelets. Switching occurs near 10 pN, a force that also induces a state of the receptor-ligand complex with slower off-rate. Force greatly increases the effects of VWD mutations, explaining pathophysiology. Conversion of single molecule kon (s(-1)) to bulk phase kon (s(-1)M(-1)) and the kon and koff values extrapolated to zero force for the low-force pathways show remarkably good agreement with bulk-phase measurements.
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Registered trials
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.