EMD-8578
Negative Stain EM of C05 mutant Fab (VPGSGW) and CR9114 Fab in complex with H1 HA Trimer
EMD-8578
Single-particle18.0 Å
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Map released: 31/05/2017
Last modified: 14/02/2018
Sample Organism:
Influenza A virus (A/Solomon Islands/3/2006(H1N1))
Sample: Negative stain EM map of C05 Mutant Fab (VPGSGW) and CR9114 fabs in complex with H1 HA trimer.
Deposition Authors: Turner HL, Ward AB
Sample: Negative stain EM map of C05 Mutant Fab (VPGSGW) and CR9114 fabs in complex with H1 HA trimer.
Deposition Authors: Turner HL, Ward AB
In vitro evolution of an influenza broadly neutralizing antibody is modulated by hemagglutinin receptor specificity.
Wu NC
,
Grande G,
Turner HL,
Ward AB,
Xie J,
Lerner RA,
Wilson IA
(2017) Nat Commun , 8 , 15371 - 15371
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(2017) Nat Commun , 8 , 15371 - 15371
Abstract:
The relatively recent discovery and characterization of human broadly neutralizing antibodies (bnAbs) against influenza virus provide valuable insights into antiviral and vaccine development. However, the factors that influence the evolution of high-affinity bnAbs remain elusive. We therefore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to H1 and H3 HAs. The C05 variants evolve up to 20-fold higher affinity but increase specificity to each HA subtype used in the selection. Structural analysis reveals that the fine specificity is strongly influenced by a highly conserved substitution that regulates receptor binding in different subtypes. Overall, this study suggests that subtle natural variations in the HA RBS between subtypes and species may differentially influence the evolution of high-affinity bnAbs.
The relatively recent discovery and characterization of human broadly neutralizing antibodies (bnAbs) against influenza virus provide valuable insights into antiviral and vaccine development. However, the factors that influence the evolution of high-affinity bnAbs remain elusive. We therefore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to H1 and H3 HAs. The C05 variants evolve up to 20-fold higher affinity but increase specificity to each HA subtype used in the selection. Structural analysis reveals that the fine specificity is strongly influenced by a highly conserved substitution that regulates receptor binding in different subtypes. Overall, this study suggests that subtle natural variations in the HA RBS between subtypes and species may differentially influence the evolution of high-affinity bnAbs.