ArticleProtein science : a publication of the Protein Society2013
The linker between the D3 and A1 domains of vWF suppresses A1-GPIbα catch bonds by site-specific binding to the A1 domain.
Article in Protein science : a publication of the Protein Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 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
- Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.Blood · 2024Article
- Autoinhibitory module underlies species difference in shear activation of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2022Article
- The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond.RSC chemical biology · 2022Article
- A p.Arg127Gln variant in GPIbα LRR5 allosterically enhances affinity for VWF: a novel form of platelet-type VWD.Blood advances · 2022Article
- Article
- Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.Nature communications · 2021Article
- Cleavage by MMP-13 renders VWF unable to bind to collagen but increases its platelet reactivity.Journal of thrombosis and haemostasis : JTH · 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
- 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
- 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
- Specific electrostatic interactions between charged amino acid residues regulate binding of von Willebrand factor to blood platelets.The Journal of biological chemistry · 2017Article
- Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients.Biophysical chemistry · 2017Article
- A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2017Article
- Enhanced Local Disorder in a Clinically Elusive von Willebrand Factor Provokes High-Affinity Platelet Clumping.Journal of molecular biology · 2017Article
- The Von Willebrand Factor A1-Collagen III Interaction Is Independent of Conformation and Type 2 Von Willebrand Disease Phenotype.Journal of molecular biology · 2017Article
- Article
- Differential surface activation of the A1 domain of von Willebrand factor.Biointerphases · 2016Article
- Data on the purification and crystallization of the loss-of-function von Willebrand disease variant (p.Gly1324Ser) of the von Willebrand factor A1 domain.Data in brief · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Platelet attachment to von Willebrand factor (vWF) requires the interaction between the platelet GP1bα and exposed vWF-A1 domains. Structural insights into the mechanism of the A1-GP1bα interaction have been limited to an N-terminally truncated A1 domain that lacks residues Q1238 - E1260 that make up the linker between the D3 and A1 domains of vWF. We have demonstrated that removal of these residues destabilizes quaternary interactions in the A1A2A3 tridomain and contributes to platelet activation under high shear (Auton et al., J Biol Chem 2012;287:14579-14585). In this study, we demonstrate that removal of these residues from the single A1 domain enhances platelet pause times on immobilized A1 under rheological shear. A rigorous comparison between the truncated A1-1261 and full length A1-1238 domains demonstrates a kinetic stabilization of the A1 domain induced by these N-terminal residues as evident in the enthalpy of the unfolding transition. This stabilization occurs through site and sequence-specific binding of the N-terminal peptide to A1. Binding of free N-terminal peptide to A1-1261 has an affinity KD=46±6μM and this binding although free to dissociate is sufficient to suppress the platelet pause times to levels comparable to A1-1238 under shear stress. Our results support a dual-structure/function role for this linker region involving a conformational equilibria that maintains quaternary A domain associations in the inactive state of vWF at low shear and an intra-A1-domain conformation that regulates the strength of platelet GP1bα-vWF A1 domain associations in the active state of vWF at high shear.
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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.