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TitlePotent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains.
Journal, issue, pagesPLoS Biol, Vol. 17, Issue 2, Page e3000139, Year 2019
Publish dateFeb 4, 2019
AuthorsHannah L Turner / Jesper Pallesen / Shanshan Lang / Sandhya Bangaru / Sarah Urata / Sheng Li / Christopher A Cottrell / Charles A Bowman / James E Crowe / Ian A Wilson / Andrew B Ward /
PubMed AbstractSeasonal 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 ...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.
External linksPLoS Biol / PubMed:30716060 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 20.0 Å
Structure data

EMDB-9139: H7 HA0 in complex with Fab from H7.5 IgG
PDB-6mlm: H7 HA0 in complex with Fv from H7.5 IgG
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-9142:
CryoEM map of cleaved H7 Shanghai in complex with H7.5 Fab
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-9143:
CryoEM map of cleaved H7 Netherlands in complex with H7.5 Fab
Method: EM (single particle) / Resolution: 9.2 Å

EMDB-9144:
Negative Stain EM map of uncleaved H7 New York in complex with H7.5 Fab
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-9145:
CryoEM map of cleaved H7 Netherlands in complex with two H7.5 Fabs
Method: EM (single particle) / Resolution: 7.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • influenza a virus (a/new york/107/2003(h7n2))
  • influenza a virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/Immune System / Hemagglutinin / antibody / Fab / H7 / HA0 / protein complex / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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