Evidence map›Paper›PMID 24391089›Full record

ArticleThe Journal of biological chemistry2014

Structural basis of regulation of von Willebrand factor binding to glycoprotein Ib.

Mark A Blenner, Xianchi Dong, Timothy A Springer

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Von Willebrand factor and hematogenous cancer metastasis under flow.Frontiers in cell and developmental biology · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. AInternational journal of molecular sciences · 2022
    Article
  11. Platelets in Non-alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Activated αeLife · 2020
    Article
  16. Article
  17. Article
  18. Article
  19. Delimiting the autoinhibitory module of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2018
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Mark A BlennerFrom the Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Xianchi Dong
Timothy A Springer
Boston Children's Hospital · US

Funding

Structures of Alpha 4 Integrins, Ligands and AntagonistsP01HL103526 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SPRINGER, TIMOTHY A · 2011 to 2015
$11.1M
Single molecule measurements on von Willebrand factor A1 and A2 domainsR01HL108248 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SPRINGER, TIMOTHY A · 2011 to 2015
$2.4M
Enabling Structural Studies of Force Activated Adhesion ComplexesF32HL099167 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI BLENNER, MARK ALAN · 2010 to 2012
$81k
NHLBI NIH HHS 1F32HL-099167NHLBI NIH HHS F32 HL099167NHLBI NIH HHS HL-103526NHLBI NIH HHS P01 HL103526NHLBI NIH HHS R01 HL108248
6 · The paper itself

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.

Indexed as

Binding SitesCrystallography, X-RayDirected Molecular EvolutionHumansMutationPlatelet Glycoprotein GPIb-IX ComplexProtein Structure, Quaternaryvon Willebrand Factoradhesion receptorPlatelet Glycoprotein GPIb-IX Complexvon Willebrand FactorDirected EvolutionGlycoprotein IbImmunologyProtein FoldingStructural Biologyvon Willebrand FactorYeast Display

Identifiers

PMID24391089
PMCPMC3937634
OpenAlexW2083806158

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.