ArticleJournal of the American Heart Association2014
Platelet GpIba binding to von Willebrand Factor under fluid shear:contributions of the D′D3-domain, A1-domain flanking peptide and O-linked glycans.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Flow molecular dynamics simulations reveal mechano-presentation of von Willebrand factor through glycan-modulated autoinhibitory modules.APL bioengineering · 2026Article
- Targeting von Willebrand factor selectively under inflammatory conditions.bioRxiv : the preprint server for biology · 2026Article
- Dynamics of a von Willebrand Factor A1 Autoinhibitory Module with O-Linked Glycans and Its Roles in Regulation of GPIbα Binding.The journal of physical chemistry. B · 2025Article
- Article
- Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.Blood · 2024Article
- Von Willebrand factor A1 domain stability and affinity for GPIbα are differentially regulated by itseLife · 2022Article
- Desialylation of O-glycans activates von Willebrand factor by destabilizing its autoinhibitory module.Journal of thrombosis and haemostasis : JTH · 2022Article
- Article
- Von Willebrand Factor Facilitates Intravascular Dissemination of MicrosporidiaFrontiers in cellular and infection microbiology · 2021Article
- Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants.Stem cell research & therapy · 2020Article
- Evidence for the Misfolding of the A1 Domain within Multimeric von Willebrand Factor in Type 2 von Willebrand Disease.Journal of molecular biology · 2020Article
- Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.Journal of thrombosis and haemostasis : JTH · 2020Article
- Gone With the Vane.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain.Blood advances · 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
- The physical spacing between the von Willebrand factor D'D3 and A1 domains regulates platelet adhesion in vitro and in vivo.Journal of thrombosis and haemostasis : JTH · 2018Article
- Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.Nature communications · 2017Article
- Review
- Role of fluid shear stress in regulating VWF structure, function and related blood disorders.Biorheology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVon Willebrand Factor (VWF) A1-domain binding to platelet receptor GpIbα is an important fluid-shear dependent interaction that regulates both soluble VWF binding to platelets, and platelet tethering onto immobilized VWF. We evaluated the roles of different structural elements at the N-terminus of the A1-domain in regulating shear dependent platelet binding. Specifically, the focus was on the VWF D'D3-domain, A1-domain N-terminal flanking peptide (NFP), and O-glycans on this peptide. METHODS AND
resultsFull-length dimeric VWF (ΔPro-VWF), dimeric VWF lacking the D'D3 domain (ΔD'D3-VWF), and ΔD'D3-VWF variants lacking either the NFP (ΔD'D3NFP(─)-VWF) or just O-glycans on this peptide (ΔD'D3OG(─)-VWF) were expressed. Monomeric VWF-A1 and D'D3-A1 were also produced. In ELISA, the apparent dissociation constant (KD) of soluble ΔPro-VWF binding to immobilized GpIbα (KD≈100 nmol/L) was 50- to 100-fold higher than other proteins lacking the D'D3 domain (KD~0.7 to 2.5 nmol/L). Additionally, in surface plasmon resonance studies, the on-rate of D'D3-A1 binding to immobilized GpIbα (kon=1.8±0.4×10(4) (mol/L)(-1)·s(-1); KD=1.7 μmol/L) was reduced compared with the single VWF-A1 domain (kon=5.1±0.4×10(4) (mol/L)(-1)·s(-1); KD=1.2 μmol/L). Thus, VWF-D'D3 primarily controls soluble VWF binding to GpIbα. In contrast, upon VWF immobilization, all molecular features regulated A1-GpIbα binding. Here, in ELISA, the number of apparent A1-domain sites available for binding GpIbα on ΔPro-VWF was ≈50% that of the ΔD'D3-VWF variants. In microfluidics based platelet adhesion measurements on immobilized VWF and thrombus formation assays on collagen, human platelet recruitment varied as ΔPro-VWF<ΔD'D3-VWF<ΔD'D3NFP(─)-VWF<ΔD'D3OG(─)-VWF.
conclusionsWhereas VWF-D'D3 is the major regulator of soluble VWF binding to platelet GpIbα, both the D'D3-domain and N-terminal peptide regulate platelet translocation and thrombus formation.
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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.