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CryoEM structure of an influenza virus receptor-binding site antibody-antigen interface

TitleCryoEM structure of an influenza virus receptor-binding site antibody-antigen interface
Publication TypeJournal Article
Year of Publication2017
AuthorsLiu, Y, Pan J, Jenni S, Raymond DD, Caradonna T, Do KT, Schmidt AG, Grigorieff N, Harrison SC
Refereed DesignationRefereed
JournalJ. Mol. Biol.
Volume429
Pagination1829–1839
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 Fv (scFv) complexes, by studying a complex we failed to crystallize in pursuing an extended project of 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-like HA 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.

DOI10.1016/j.jmb.2017.05.011
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