2YPG

Haemagglutinin of 1968 Human H3N2 Virus in Complex with Human Receptor Analogue LSTc


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Evolution of the Receptor Binding Properties of the Influenza A(H3N2) Hemagglutinin.

Lin, Y.P.Xiong, X.Wharton, S.A.Martin, S.R.Coombs, P.J.Vachieri, S.G.Christodoulou, E.Walker, P.A.Liu, J.Skehel, J.J.Gamblin, S.J.Hay, A.J.Daniels, R.S.Mccauley, J.W.

(2012) Proc Natl Acad Sci U S A 109: 21474

  • DOI: https://doi.org/10.1073/pnas.1218841110
  • Primary Citation of Related Structures:  
    2YP2, 2YP3, 2YP4, 2YP5, 2YP7, 2YP8, 2YP9, 2YPG

  • PubMed Abstract: 

    The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). By 2001, the avidity of human H3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. These changes in receptor binding, which correlate with increased difficulties in virus propagation in vitro and in antigenic analysis, have been assessed by virus hemagglutination of erythrocytes from different species and quantified by measuring virus binding to receptor analogs using surface biolayer interferometry. Crystal structures of HA-receptor analog complexes formed with HAs from viruses isolated in 2004 and 2005 reveal significant differences in the conformation of the 220-loop of HA1, relative to the 1968 structure, resulting in altered interactions between the HA and the receptor analog that explain the changes in receptor affinity. Site-specific mutagenesis shows the HA1 Asp-225→Asn substitution to be the key determinant of the decreased receptor binding in viruses circulating since 2005. Our results indicate that the evolution of human influenza A(H3N2) viruses since 1968 has produced a virus with a low propensity to bind human receptor analogs, and this loss of avidity correlates with the marked reduction in A(H3N2) virus disease impact in the last 10 y.


  • Organizational Affiliation

    Division of Virology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEMAGGLUTININ HA1 CHAIN
A, C, E
328Influenza A virus (A/X-31(H3N2))Mutation(s): 0 
UniProt
Find proteins for P03437 (Influenza A virus (strain A/Aichi/2/1968 H3N2))
Explore P03437 
Go to UniProtKB:  P03437
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03437
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HEMAGGLUTININ HA2 CHAIN
B, D, F
175Influenza A virus (A/X-31(H3N2))Mutation(s): 0 
UniProt
Find proteins for P03437 (Influenza A virus (strain A/Aichi/2/1968 H3N2))
Explore P03437 
Go to UniProtKB:  P03437
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03437
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose
G
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G28454KX
GlyCosmos:  G28454KX
GlyGen:  G28454KX
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
H, M
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
I, K, L, N, Q
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose
J, R
5N/A
Glycosylation Resources
GlyTouCan:  G83513YI
GlyCosmos:  G83513YI
GlyGen:  G83513YI
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose
O
4N/A
Glycosylation Resources
GlyTouCan:  G03509EL
GlyCosmos:  G03509EL
GlyGen:  G03509EL
Entity ID: 8
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose
P
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G53081KU
GlyCosmos:  G53081KU
GlyGen:  G53081KU
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
CA [auth D],
EA [auth E],
IA [auth F],
S [auth A],
Y [auth C]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
FLC
Query on FLC

Download Ideal Coordinates CCD File 
AA [auth C]
BA [auth C]
DA [auth D]
FA [auth E]
GA [auth E]
AA [auth C],
BA [auth C],
DA [auth D],
FA [auth E],
GA [auth E],
HA [auth E],
JA [auth F],
T [auth A],
U [auth A],
V [auth B],
W [auth B],
X [auth B],
Z [auth C]
CITRATE ANION
C6 H5 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 160.767α = 90
b = 160.767β = 90
c = 177.21γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
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: 2012-11-07
    Type: Initial release
  • Version 1.1: 2012-12-26
    Changes: Database references, Structure summary
  • Version 1.2: 2013-01-16
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary