4FQR

Crystal structure of broadly neutralizing antibody C05 bound to H3 influenza hemagglutinin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.10 Å
  • R-Value Free: 0.334 
  • R-Value Work: 0.309 
  • R-Value Observed: 0.310 

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Ligand Structure Quality Assessment 


This is version 3.2 of the entry. See complete history


Literature

Cross-neutralization of influenza A viruses mediated by a single antibody loop.

Ekiert, D.C.Kashyap, A.K.Steel, J.Rubrum, A.Bhabha, G.Khayat, R.Lee, J.H.Dillon, M.A.O'Neil, R.E.Faynboym, A.M.Horowitz, M.Horowitz, L.Ward, A.B.Palese, P.Webby, R.Lerner, R.A.Bhatt, R.R.Wilson, I.A.

(2012) Nature 489: 526-532

  • DOI: https://doi.org/10.1038/nature11414
  • Primary Citation of Related Structures:  
    4FNK, 4FNL, 4FP8, 4FQR

  • PubMed Abstract: 

    Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1 chain
A, C, E, G, I
A, C, E, G, I, K, M, O, Q, S, U, W
323Influenza A virus (A/Hong Kong/1/1968(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2))
Explore Q91MA7 
Go to UniProtKB:  Q91MA7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91MA7
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA2 chain
B, D, F, H, J
B, D, F, H, J, L, N, P, R, T, V, X
174Influenza A virus (A/Hong Kong/1/1968(H3N2))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2))
Explore Q91MA7 
Go to UniProtKB:  Q91MA7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91MA7
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Broadly neutralizing antibody C05, heavy chain241Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Broadly neutralizing antibody C05, light chain214Homo sapiensMutation(s): 0 
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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
AB [auth 0],
CB [auth 2],
EB [auth 4],
GB [auth 6],
IB [auth 8],
AB [auth 0],
CB [auth 2],
EB [auth 4],
GB [auth 6],
IB [auth 8],
KB [auth AA],
MB [auth CA],
OB [auth EA],
QB [auth GA],
SB [auth IA],
WA [auth Y],
YA [auth y]
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22573RC
GlyCosmos:  G22573RC
GlyGen:  G22573RC
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
BB [auth 1],
DB [auth 3],
FB [auth 5],
HB [auth 7],
JB [auth 9],
BB [auth 1],
DB [auth 3],
FB [auth 5],
HB [auth 7],
JB [auth 9],
LB [auth BA],
NB [auth DA],
PB [auth FA],
RB [auth HA],
TB [auth JA],
XA [auth Z],
ZA [auth z]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AC [auth G]
BC [auth G]
CC [auth H]
DC [auth I]
EC [auth J]
AC [auth G],
BC [auth G],
CC [auth H],
DC [auth I],
EC [auth J],
FC [auth K],
GC [auth L],
HC [auth M],
IC [auth M],
JC [auth N],
KC [auth O],
LC [auth O],
MC [auth P],
NC [auth Q],
OC [auth Q],
PC [auth R],
QC [auth S],
RC [auth S],
SC [auth T],
TC [auth U],
UB [auth A],
UC [auth U],
VB [auth B],
VC [auth V],
WB [auth C],
WC [auth W],
XB [auth D],
XC [auth X],
YB [auth E],
ZB [auth F]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
AA [auth c]
CA [auth e]
EA [auth g]
GA [auth i]
IA [auth k]
AA [auth c],
CA [auth e],
EA [auth g],
GA [auth i],
IA [auth k],
KA [auth m],
MA [auth o],
OA [auth q],
QA [auth s],
SA [auth u],
UA [auth w],
Y [auth a]
L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.10 Å
  • R-Value Free: 0.334 
  • R-Value Work: 0.309 
  • R-Value Observed: 0.310 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 142.02α = 89.95
b = 158.62β = 85.44
c = 178.5γ = 84.37
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
XPREPdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-19
    Type: Initial release
  • Version 1.1: 2012-10-03
    Changes: Database references
  • Version 1.2: 2012-10-10
    Changes: Database references
  • Version 2.0: 2019-12-25
    Changes: Database references, Derived calculations, Polymer sequence
  • Version 3.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Other, Structure summary
  • Version 3.1: 2021-05-19
    Changes: Derived calculations, Source and taxonomy, Structure summary
  • Version 3.2: 2023-09-13
    Changes: Data collection, Database references, Refinement description