6MLM

H7 HA0 in complex with Fv from H7.5 IgG

Summary for 6MLM

• Entry DOI: 10.2210/pdb6mlm/pdb
• EMDB information: 9139
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Heavy chain Fv of H7.5 Fab, ... (5 entities in total)
• Functional Keywords: hemagglutinin, antibody, fab, h7, ha0, protein complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/New York/107/2003(H7N2)); More
• Total number of polymer chains: 12
• Total formula weight: 327145.45

Authors

Pallesen, J.,Turner, H.L.,Ward, A.B. (deposition date: 2018-09-27, release date: 2019-02-20, Last modification date: 2024-10-09)

Primary citation

Turner, H.L.,Pallesen, J.,Lang, S.,Bangaru, S.,Urata, S.,Li, S.,Cottrell, C.A.,Bowman, C.A.,Crowe Jr., J.E.,Wilson, I.A.,Ward, A.B.
Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains.
PLoS Biol., 17:e3000139-e3000139, 2019

PubMed Abstract: 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.

PubMed: 30716060
DOI: 10.1371/journal.pbio.3000139

Experimental method

ELECTRON MICROSCOPY (3.5 Å)