4GMS

Crystal structure of heterosubtypic Fab S139/1 in complex with influenza A H3 hemagglutinin

Summary for 4GMS

• Entry DOI: 10.2210/pdb4gms/pdb
• Related: 4GMT
• Descriptor: Hemagglutinin HA1 chain, SULFATE ION, GLYCEROL, ... (13 entities in total)
• Functional Keywords: immunoglobulin, virus attachment and entry, immune recognition, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 322730.50

Authors

Lee, P.S.,Ekiert, D.C.,Wilson, I.A. (deposition date: 2012-08-16, release date: 2012-10-03, Last modification date: 2024-11-20)

Primary citation

Lee, P.S.,Yoshida, R.,Ekiert, D.C.,Sakai, N.,Suzuki, Y.,Takada, A.,Wilson, I.A.
Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity.
Proc.Natl.Acad.Sci.USA, 109:17040-17045, 2012

PubMed Abstract: Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes.

PubMed: 23027945
DOI: 10.1073/pnas.1212371109

Experimental method

X-RAY DIFFRACTION (2.95 Å)