ArticleBlood2016
N-linked glycan stabilization of the VWF A2 domain.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Conformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.NAR molecular medicine · 2024Article
- Desialylation of O-glycans activates von Willebrand factor by destabilizing its autoinhibitory module.Journal of thrombosis and haemostasis : JTH · 2022Article
- PD-L2 glycosylation promotes immune evasion and predicts anti-EGFR efficacy.Journal for immunotherapy of cancer · 2021Article
- Stereoelectronic effects in stabilizing protein-N-glycan interactions revealed by experiment and machine learning.Nature chemistry · 2021Article
- The relationship between ABO blood group, von Willebrand factor, and primary hemostasis.Blood · 2020Review
- 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
- Enhanced activity of an ADAMTS-13 variant (R568K/F592Y/R660K/Y661F/Y665F) against platelet agglutination in vitro and in a murine model of acute ischemic stroke.Journal of thrombosis and haemostasis : JTH · 2018Article
- Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.Scientific reports · 2018Article
- Delimiting the autoinhibitory module of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2018Article
- Autoregulation of von Willebrand factor function by a disulfide bond switch.Science advances · 2018Article
- ADAMTS-13 and von Willebrand factor: a dynamic duo.Journal of thrombosis and haemostasis : JTH · 2018Review
- An Insight into Glyco-Microheterogeneity of Plasma von Willebrand Factor by Mass Spectrometry.Journal of proteome research · 2017Article
- A model for the conformational activation of the structurally quiescent metalloprotease ADAMTS13 by von Willebrand factor.The Journal of biological chemistry · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Shear forces in the blood trigger a conformational transition in the von Willebrand factor (VWF) A2 domain, from its native folded to an unfolded state, in which the cryptic scissile bond (Y1605-M1606) is exposed and can then be proteolysed by ADAMTS13. The conformational transition depends upon a Ca(2+)binding site and a vicinal cysteine disulfide bond. Glycosylation at N1574 has previously been suggested to modulate VWF A2 domain interaction with ADAMTS13 through steric hindrance by the bulky carbohydrate structure. We investigated how the N-linked glycans of the VWF A2 domain affect thermostability and regulate both the exposure of the ADAMTS13 binding sites and the scissile bond. We show by differential scanning fluorimetry that the N-linked glycans thermodynamically stabilize the VWF A2 domain. The essential component of the glycan structure is the first sugar residue (GlcNAc) at the N1574 attachment site. From its crystal structures, N1574-GlcNAc is predicted to form stabilizing intradomain interactions with Y1544 and nearby residues. Substitution of the surface-exposed Y1544 to aspartic acid is able to stabilize the domain in the absence of glycosylation and protect against ADAMTS13 proteolysis in both the VWF A2 domain and FLVWF. Glycan stabilization of the VWF A2 domain acts together with the Ca(2+)binding site and vicinal cysteine disulfide bond to control unfolding and ADAMTS13 proteolysis.
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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.