6FWN

Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor.

Xu, E.R.von Bulow, S.Chen, P.C.Lenting, P.J.Kolsek, K.Aponte-Santamaria, C.Simon, B.Foot, J.Obser, T.Schneppenheim, R.Grater, F.Denis, C.V.Wilmanns, M.Hennig, J.

(2019) Blood 133: 366-376

  • DOI: https://doi.org/10.1182/blood-2018-04-843615
  • Primary Citation of Related Structures:  
    6FWN

  • PubMed Abstract: 

    Von Willebrand factor (VWF) is a key player in the regulation of hemostasis by promoting recruitment of platelets to sites of vascular injury. An array of 6 C domains forms the dimeric C-terminal VWF stem. Upon shear force activation, the stem adopts an open conformation allowing the adhesion of VWF to platelets and the vessel wall. To understand the underlying molecular mechanism and associated functional perturbations in disease-related variants, knowledge of high-resolution structures and dynamics of C domains is of paramount interest. Here, we present the solution structure of the VWF C4 domain, which binds to the platelet integrin and is therefore crucial for the VWF function. In the structure, we observed 5 intra- and inter-subdomain disulfide bridges, of which 1 is unique in the C4 domain. The structure further revealed an unusually hinged 2-subdomain arrangement. The hinge is confined to a very short segment around V2547 connecting the 2 subdomains. Together with 2 nearby inter-subdomain disulfide bridges, this hinge induces slow conformational changes and positional alternations of both subdomains with respect to each other. Furthermore, the structure demonstrates that a clinical gain-of-function VWF variant (Y2561) is more likely to have an effect on the arrangement of the C4 domain with neighboring domains rather than impairing platelet integrin binding.


  • Organizational Affiliation

    Hamburg Unit, European Molecular Biology Laboratory, Hamburg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
von Willebrand factor85Homo sapiensMutation(s): 0 
Gene Names: VWFF8VWF
UniProt & NIH Common Fund Data Resources
Find proteins for P04275 (Homo sapiens)
Explore P04275 
Go to UniProtKB:  P04275
PHAROS:  P04275
GTEx:  ENSG00000110799 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04275
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-24
    Type: Initial release
  • Version 1.1: 2019-02-06
    Changes: Data collection, Database references
  • Version 1.2: 2019-05-08
    Changes: Data collection