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PDBsum entry 4gmt
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Immune system
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PDB id
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4gmt
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References listed in PDB file
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Key reference
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Title
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Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity.
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Authors
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P.S.Lee,
R.Yoshida,
D.C.Ekiert,
N.Sakai,
Y.Suzuki,
A.Takada,
I.A.Wilson.
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Ref.
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Proc Natl Acad Sci U S A, 2012,
109,
17040-17045.
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PubMed id
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Abstract
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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.
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