3D12

Crystal Structures of Nipah Virus G Attachment Glycoprotein in Complex with its Receptor Ephrin-B3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.221 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3.

Xu, K.Rajashankar, K.R.Chan, Y.P.Himanen, J.P.Broder, C.C.Nikolov, D.B.

(2008) Proc Natl Acad Sci U S A 105: 9953-9958

  • DOI: https://doi.org/10.1073/pnas.0804797105
  • Primary Citation of Related Structures:  
    3D11, 3D12

  • PubMed Abstract: 

    Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G beta-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin-neuraminidaseA,
C [auth D]
428Henipavirus nipahenseMutation(s): 0 
Gene Names: HN
EC: 3.2.1.18
UniProt
Find proteins for Q9IH62 (Nipah virus)
Explore Q9IH62 
Go to UniProtKB:  Q9IH62
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9IH62
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ephrin-B3B,
D [auth E]
141Mus musculusMutation(s): 0 
Gene Names: Efnb3
UniProt
Find proteins for O35393 (Mus musculus)
Explore O35393 
Go to UniProtKB:  O35393
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO35393
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseE [auth C]5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42769XG
GlyCosmos:  G42769XG
GlyGen:  G42769XG
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-glucopyranose-(1-3)-[alpha-D-glucopyranose-(1-6)]beta-D-gulopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-[beta-D-glucopyranose-(1-3)][alpha-D-glucopyranose-(1-6)]2-acetamido-2-deoxy-alpha-D-idopyranose
F
7N/A
Glycosylation Resources
GlyTouCan:  G63190SA
GlyCosmos:  G63190SA
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
G, J
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-glucopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
H
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G47515FY
GlyCosmos:  G47515FY
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-glucopyranose-(1-3)-[alpha-D-glucopyranose-(1-6)]beta-D-gulopyranose-(1-4)-2-acetamido-2-deoxy-alpha-L-glucopyranose-(1-4)-[beta-D-glucopyranose-(1-3)][alpha-L-galactopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-gulopyranose
I
7N/A
Glycosylation Resources
GlyTouCan:  G52818VR
GlyCosmos:  G52818VR
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
K [auth A],
W [auth D]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth D]
CA [auth D]
DA [auth D]
EA [auth D]
AA [auth D],
BA [auth D],
CA [auth D],
DA [auth D],
EA [auth D],
FA [auth D],
GA [auth D],
HA [auth E],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth B],
V [auth B],
X [auth D],
Y [auth D],
Z [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.221 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 189.492α = 90
b = 189.492β = 90
c = 277.052γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
PHASESphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2014-02-12
    Changes: Atomic model
  • Version 1.3: 2017-10-25
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary