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PDBsum entry 1eo8

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Viral protein/immune system PDB id
1eo8
Jmol
Contents
Protein chains
319 a.a. *
175 a.a. *
210 a.a. *
217 a.a. *
Ligands
NAG ×2
NAG-NAG-MAN
NAG-NAG
Waters ×109
* Residue conservation analysis
PDB id:
1eo8
Name: Viral protein/immune system
Title: Influenza virus hemagglutinin complexed with a neutralizing
Structure: Hemagglutinin (ha1 chain). Chain: a. Fragment: bromelain released fragment. Other_details: a recombinant influenza strain containing a/ (h3n2) hemagglutinin. Hemagglutinin (ha2 chain). Chain: b. Fragment: bromelain released fragment. Other_details: a recombinant influenza strain containing a/
Source: Influenza a virus (a/x-31(h3n2)). Organism_taxid: 132504. Strain: x31. Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Cell: hybridromas. Cell: hybridromas
Biol. unit: Dodecamer (from PDB file)
Resolution:
2.80Å     R-factor:   0.196     R-free:   0.298
Authors: D.Fleury,B.Gigant,R.S.Daniels,J.J.Skehel,M.Knossow,T.Bizebar
Key ref:
D.Fleury et al. (2000). Structural evidence for recognition of a single epitope by two distinct antibodies. Proteins, 40, 572-578. PubMed id: 10899782 DOI: 10.1002/1097-0134(20000901)40:4<572::AID-PROT30>3.3.CO;2-E
Date:
22-Mar-00     Release date:   12-Apr-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03437  (HEMA_I68A0) -  Hemagglutinin
Seq:
Struc:
 
Seq:
Struc:
566 a.a.
319 a.a.
Protein chain
Pfam   ArchSchema ?
P03437  (HEMA_I68A0) -  Hemagglutinin
Seq:
Struc:
 
Seq:
Struc:
566 a.a.
175 a.a.
Protein chain
No UniProt id for this chain
Struc: 210 a.a.
Protein chain
No UniProt id for this chain
Struc: 217 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     viral envelope   1 term 
  Biological process     viral envelope fusion with host membrane   1 term 
  Biochemical function     host cell surface receptor binding     1 term  

 

 
DOI no: 10.1002/1097-0134(20000901)40:4<572::AID-PROT30>3.3.CO;2-E Proteins 40:572-578 (2000)
PubMed id: 10899782  
 
 
Structural evidence for recognition of a single epitope by two distinct antibodies.
D.Fleury, R.S.Daniels, J.J.Skehel, M.Knossow, T.Bizebard.
 
  ABSTRACT  
 
The structure of a complex between the hemagglutinin of influenza virus and the Fab of a neutralizing antibody was determined by X-ray crystallography at 2.8 A resolution. This antibody and another which has only 56% sequence identity bind to the same epitope with very similar affinities and in the same orientation. One third of the interactions is conserved in the two complexes; a significant proportion of the interactions that differ are established by residues of the H3 complementarity-determining regions (CDR) which adopt distinct conformations in the two antibodies. This demonstrates that there is a definite flexibility in the selection of antibodies that bind to a given epitope, despite the high affinity of their complexes. This flexibility allows the humoral immune response to be redundant, a feature that may be useful in achieving longer lasting protection against evolving viral pathogens.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. X31 HA-BH151 Fab and X31 HA-HC45 Fab complexes. a. ribbon diagram of the BHA X31-BH151 Fab complex. One BHA monomer is shown (HA[1] in blue, HA[2] in red) and the Fab is in green. All figures were drawn with Molscript[43] and Raster3D.[44] b. stereo view of the BH151-HA interface: HA[1] residues are in blue and Fab residues are in green. Nitrogen and oxygen atoms are color-coded according to their atomic type. Hydrogen bonds between antigen and antibody, and those stabilizing the conformation of the side chain H94 (see text) are shown as dotted lines. For clarity, only those residues most buried at the antibody-antigen interface are displayed: they are involved in 70% of the atomic pair contacts between antibody and antigen. c. and d- HA epitopes recognized by HC45 and BH151. The BHA monomer (HA[1] blue, HA[2] red) is pictured as a CPK model. The epitopes (green and yellow) recognized by HC45 and BH151 are presented in (c) and (d), respectively. Residue HA[1] 63 (common to both epitopes and involved in the sole salt bridge between the two complexes) is highlighted in orange.
Figure 2.
Figure 2. Conformations of the H3 CDR in HC45 and BH151. H3 CDR polypeptide chains are shown in pale grey (BH151) and black (HC45) after superposition of the two complexes. Residue H94 Arg, on H3 CDR edge, conserved in the two Fabs and spatially superimposable in the two complexes is also displayed. Due to their different conformations, the H3 CDRs in the two Fabs interact differently with HA. Residue HA[1] 78 (in grey, the HA[1] 74-82 polypeptide chain is also displayed) provides an example of these differences: the C s of the Fab residues it interacts with predominantly are distant by 8 Å when the two complexes are superimposed.
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2000, 40, 572-578) copyright 2000.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22982990 D.C.Ekiert, A.K.Kashyap, J.Steel, A.Rubrum, G.Bhabha, R.Khayat, J.H.Lee, M.A.Dillon, R.E.O'Neil, A.M.Faynboym, M.Horowitz, L.Horowitz, A.B.Ward, P.Palese, R.Webby, R.A.Lerner, R.R.Bhatt, and I.A.Wilson (2012).
Cross-neutralization of influenza A viruses mediated by a single antibody loop.
  Nature, 489, 526-532.
PDB codes: 4fnk 4fnl 4fp8 4fqr
21067544 Y.El-Manzalawy, and V.Honavar (2010).
Recent advances in B-cell epitope prediction methods.
  Immunome Res, 6, S2.  
19251591 D.C.Ekiert, G.Bhabha, M.A.Elsliger, R.H.Friesen, M.Jongeneelen, M.Throsby, J.Goudsmit, and I.A.Wilson (2009).
Antibody recognition of a highly conserved influenza virus epitope.
  Science, 324, 246-251.
PDB codes: 3gbm 3gbn
18359855 L.Berglund, J.Andrade, J.Odeberg, and M.Uhlén (2008).
The epitope space of the human proteome.
  Protein Sci, 17, 606-613.  
18234071 V.Moreau, C.Fleury, D.Piquer, C.Nguyen, N.Novali, S.Villard, D.Laune, C.Granier, and F.Molina (2008).
PEPOP: computational design of immunogenic peptides.
  BMC Bioinformatics, 9, 71.  
18032723 X.Du, Z.Wang, A.Wu, L.Song, Y.Cao, H.Hang, and T.Jiang (2008).
Networks of genomic co-occurrence capture characteristics of human influenza A (H3N2) evolution.
  Genome Res, 18, 178-187.  
17910770 J.V.Ponomarenko, and P.E.Bourne (2007).
Antibody-protein interactions: benchmark datasets and prediction tools evaluation.
  BMC Struct Biol, 7, 64.  
17585869 M.A.Zhukovsky, I.Markovic, and A.L.Bailey (2007).
Influence of calcium on lipid mixing mediated by influenza hemagglutinin.
  Arch Biochem Biophys, 465, 101-108.  
17301785 T.Zhou, L.Xu, B.Dey, A.J.Hessell, D.Van Ryk, S.H.Xiang, X.Yang, M.Y.Zhang, M.B.Zwick, J.Arthos, D.R.Burton, D.S.Dimitrov, J.Sodroski, R.Wyatt, G.J.Nabel, and P.D.Kwong (2007).
Structural definition of a conserved neutralization epitope on HIV-1 gp120.
  Nature, 445, 732-737.
PDB codes: 2nxy 2nxz 2ny0 2ny1 2ny2 2ny3 2ny4 2ny5 2ny6 2ny7
17001032 P.Haste Andersen, M.Nielsen, and O.Lund (2006).
Prediction of residues in discontinuous B-cell epitopes using protein 3D structures.
  Protein Sci, 15, 2558-2567.  
  15150594 J.Krauss, M.A.Arndt, Z.Zhu, D.L.Newton, B.K.Vu, V.Choudhry, R.Darbha, X.Ji, N.S.Courtenay-Luck, M.P.Deonarain, J.Richards, and S.M.Rybak (2004).
Impact of antibody framework residue VH-71 on the stability of a humanised anti-MUC1 scFv and derived immunoenzyme.
  Br J Cancer, 90, 1863-1870.  
12784374 D.W.Ritchie (2003).
Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2.
  Proteins, 52, 98.  
11468348 P.V.Afonin, A.V.Fokin, I.N.Tsygannik, I.Y.Mikhailova, L.V.Onoprienko, I.I.Mikhaleva, V.T.Ivanov, T.Y.Mareeva, V.A.Nesmeyanov, N.Li, W.A.Pangborn, W.L.Duax, and V.Z.Pletnev (2001).
Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide.
  Protein Sci, 10, 1514-1521.
PDB code: 1f90
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.