James Crowe
Faculty Member
Last active: 3/31/2019

Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains.

Turner HL, Pallesen J, Lang S, Bangaru S, Urata S, Li S, Cottrell CA, Bowman CA, Crowe JE, Wilson IA, Ward AB
PLoS Biol. 2019 17 (2): e3000139

PMID: 30716060 · PMCID: PMC6375650 · DOI:10.1371/journal.pbio.3000139

Seasonal influenza virus infections can cause significant morbidity and mortality, but the threat from the emergence of a new pandemic influenza strain might have potentially even more devastating consequences. As such, there is intense interest in isolating and characterizing potent neutralizing antibodies that target the hemagglutinin (HA) viral surface glycoprotein. Here, we use cryo-electron microscopy (cryoEM) to decipher the mechanism of action of a potent HA head-directed monoclonal antibody (mAb) bound to an influenza H7 HA. The epitope of the antibody is not solvent accessible in the compact, prefusion conformation that typifies all HA structures to date. Instead, the antibody binds between HA head protomers to an epitope that must be partly or transiently exposed in the prefusion conformation. The "breathing" of the HA protomers is implied by the exposure of this epitope, which is consistent with metastability of class I fusion proteins. This structure likely therefore represents an early structural intermediate in the viral fusion process. Understanding the extent of transient exposure of conserved neutralizing epitopes also may lead to new opportunities to combat influenza that have not been appreciated previously.

MeSH Terms (23)

Amino Acid Sequence Animals Antibodies, Neutralizing Antibody Specificity Baculoviridae Binding Sites Cloning, Molecular Cryoelectron Microscopy Gene Expression Hemagglutinin Glycoproteins, Influenza Virus Hydrogen Bonding Immunoglobulin Fab Fragments Influenza A virus Molecular Docking Simulation Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs Recombinant Proteins Sequence Alignment Sequence Homology, Amino Acid Sf9 Cells Spodoptera

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