Trial reportThe Journal of biological chemistry2012
N-terminal flanking region of A1 domain in von Willebrand factor stabilizes structure of A1A2A3 complex and modulates platelet activation under shear stress.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- The N-terminal flanking region of the A1 domain regulates the force-dependent binding of von Willebrand factor to platelet glycoprotein Ibα.The Journal of biological chemistry · 2013Trial
- 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
- Structure-resolved dynamics of type 2M von Willebrand disease.Journal of thrombosis and haemostasis : JTH · 2025Article
- Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.Blood · 2024Article
- The interplay between adsorption and aggregation of von Willebrand factor chains in shear flows.Biophysical journal · 2023Article
- The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond.RSC chemical biology · 2022Article
- 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
- 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
- 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
- In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion.Journal of thrombosis and haemostasis : JTH · 2019Article
- Review
- 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
- Autoregulation of von Willebrand factor function by a disulfide bond switch.Science advances · 2018Article
- Receptor-mediated cell mechanosensing.Molecular biology of the cell · 2017Review
- A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2017Article
- The functions of the A1A2A3 domains in von Willebrand factor include multimerin 1 binding.Thrombosis and haemostasis · 2016Article
- Differential surface activation of the A1 domain of von Willebrand factor.Biointerphases · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
von Willebrand factor (vWF) mediates platelet adhesion and thrombus formation via its interaction with the platelet receptor glycoprotein (GP)Ibα. We have analyzed two A1A2A3 tri-domain proteins to demonstrate that the amino acid sequence, Gln(1238)-Glu(1260), in the N-terminal flanking region of the A1 domain, together with the association between the A domains, modulates vWF-GPIbα binding and platelet activation under shear stress. Using circular dichroism spectroscopy and differential scanning calorimetry, we have described that sequence Gln(1238)-Glu(1260) stabilizes the structural conformation of the A1A2A3 tri-domain complex. The structural stabilization imparted by this particular region inhibits the binding capacity of the tri-domain protein for GPIbα. Deletion of this region causes a conformational change in the A1 domain that increases binding to GPIbα. Only the truncated protein was capable of effectively blocking ristocetin-induced platelet agglutination. To determine the capacity of activating platelets via the interaction with GPIbα, whole blood was incubated with the N-terminal region truncated or intact tri-A domain protein prior to perfusion over a fibrin(ogen)-coated surface. At a high shear rate of 1,500 s(-1), platelets from blood containing the truncated protein rapidly bound, covering >90% of the fibrin(ogen) surface area, whereas the intact tri-A domain protein induced platelets to bind <10%. The results obtained in this study ascertain the relevant role of the structural association between the N-terminal flanking region of the A1 domain (amino acids Gln(1238)-Glu(1260)) and the A1A2A3 domain complex in preventing vWF to bind spontaneously to GPIbα in solution under high shear forces.
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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.