4V3D

The CIDRa domain from HB3var03 PfEMP1 bound to endothelial protein C receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.224 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Structural Conservation Despite Huge Sequence Diversity Allows Epcr Binding by the Pfemp1 Family Implicated in Severe Childhood Malaria.

Lau, C.K.Y.Turner, L.Jespersen, J.S.Lowe, E.D.Petersen, B.Wang, C.W.Petersen, J.E.V.Lusingu, J.Theander, T.G.Lavstsen, T.Higgins, M.K.

(2015) Cell Host Microbe 17: 118

  • DOI: https://doi.org/10.1016/j.chom.2014.11.007
  • Primary Citation of Related Structures:  
    4V3D, 4V3E

  • PubMed Abstract: 

    The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.


  • Organizational Affiliation

    Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HB3VAR03 CIDRA DOMAIN
A, C
251Plasmodium falciparum HB3Mutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ENDOTHELIAL PROTEIN C RECEPTOR
B, D
170Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UNN8 (Homo sapiens)
Explore Q9UNN8 
Go to UniProtKB:  Q9UNN8
PHAROS:  Q9UNN8
GTEx:  ENSG00000101000 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UNN8
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E, G, I
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
F, H
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G62182OO
GlyCosmos:  G62182OO
GlyGen:  G62182OO
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.224 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.13α = 90
b = 94.67β = 90
c = 290.7γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-17
    Type: Initial release
  • Version 1.1: 2014-12-24
    Changes: Database references
  • Version 1.2: 2015-01-28
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Other, Structure summary
  • Version 2.1: 2024-01-10
    Changes: Data collection, Database references, Refinement description, Structure summary