4O5I

Crystal structure of broadly neutralizing antibody F045-092 in complex with A/Victoria/361/2011 (H3N2) influenza hemagglutinin

Summary for 4O5I

• Entry DOI: 10.2210/pdb4o5i/pdb
• Related: 4O58
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Fab F045-092 heavy chain, ... (9 entities in total)
• Functional Keywords: immunoglobulin, virus attachment and entry, immune recognition, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 24
• Total formula weight: 649141.81

Authors

Lee, P.S.,Wilson, I.A. (deposition date: 2013-12-19, release date: 2014-04-16, Last modification date: 2024-04-03)

Primary citation

Lee, P.S.,Ohshima, N.,Stanfield, R.L.,Yu, W.,Iba, Y.,Okuno, Y.,Kurosawa, Y.,Wilson, I.A.
Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus.
Nat Commun, 5:3614-3614, 2014

PubMed Abstract: Influenza viruses present a significant health challenge each year, as in the H3N2 epidemic of 2012-2013. Here we describe an antibody, F045-092, that possesses broadly neutralizing activity against the entire H3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. Crystal structures of F045-092 in complex with HAs from 1975 and 2011 H3N2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23-residue HCDR3 into the receptor-binding site that involves striking receptor mimicry. F045-092 extends its recognition to divergent subtypes, including H1, H2 and H13, using the enhanced avidity of its IgG to overcome lower-affinity Fab binding, as observed with other antibodies that target the receptor-binding site. This unprecedented level of antibody cross-reactivity against the H3 subtype can potentially inform on development of a pan-H3 vaccine or small-molecule therapeutics.

PubMed: 24717798
DOI: 10.1038/ncomms4614

Experimental method

X-RAY DIFFRACTION (6.501 Å)