ArticleThe Journal of biological chemistry2014
Structural basis of regulation of von Willebrand factor binding to glycoprotein Ib.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 75 citations in OpenAlex.
- Role of von Willebrand factor (VWF), platelets, and aberrant flow in the initiation of venous thrombosis.Science advances · 2025Article
- Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.Blood advances · 2025Article
- Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.Blood · 2024Article
- Biology of factor XI.Blood · 2024Review
- Type 2M/2A von Willebrand disease: a shared phenotype between type 2M and 2A.Blood advances · 2024Article
- Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024Review
- Molecular mechanisms of catch bonds and their implications for platelet hemostasis.Biophysical reviews · 2023Review
- Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain.Blood · 2023Article
- Von Willebrand factor A1 domain stability and affinity for GPIbα are differentially regulated by itseLife · 2022Article
- AInternational journal of molecular sciences · 2022Article
- Platelets in Non-alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2022Review
- Single-molecule imaging of von Willebrand factor reveals tension-dependent self-association.Blood · 2021Article
- Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.Nature communications · 2021Article
- DNA binds to a specific site of the adhesive blood-protein von Willebrand factor guided by electrostatic interactions.Nucleic acids research · 2020Article
- Activated αeLife · 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
- Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer.Nature medicine · 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
- Delimiting the autoinhibitory module of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2018Article
- Coarse-Grain Modeling of Shear-Induced Binding between von Willebrand Factor and Collagen.Biophysical journal · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation by elongational flow of von Willebrand factor (VWF) is critical for primary hemostasis. Mutations causing type 2B von Willebrand disease (VWD), platelet-type VWD (PT-VWD), and tensile force each increase affinity of the VWF A1 domain and platelet glycoprotein Ibα (GPIbα) for one another; however, the structural basis for these observations remains elusive. Directed evolution was used to discover a further gain-of-function mutation in A1 that shifts the long range disulfide bond by one residue. We solved multiple crystal structures of this mutant A1 and A1 containing two VWD mutations complexed with GPIbα containing two PT-VWD mutations. We observed a gained interaction between A1 and the central leucine-rich repeats (LRRs) of GPIbα, previously shown to be important at high shear stress, and verified its importance mutationally. These findings suggest that structural changes, including central GPIbα LRR-A1 contact, contribute to VWF affinity regulation. Among the mutant complexes, variation in contacts and poor complementarity between the GPIbα β-finger and the region of A1 harboring VWD mutations lead us to hypothesize that the structures are on a pathway to, but have not yet reached, a force-induced super high affinity state.
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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.