CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen Interface

Journal of Molecular Biology
Yuhang LiuNikolaus Grigorieff

Abstract

Structure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5Å.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants.

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Jan 10, 2020·Virologica Sinica·Na LiSheng Cao
Mar 30, 2018·Annual Review of Biophysics·Max CrispinIan A Wilson
Apr 14, 2018·Acta Crystallographica. Section D, Structural Biology·Paul Emsley, Max Crispin
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Apr 9, 2020·ACS Infectious Diseases·Goran BajicAaron G Schmidt
Jun 10, 2020·Cold Spring Harbor Perspectives in Medicine·Steven J GamblinJohn J Skehel

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