4NM8

Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin

Summary for 4NM8

• Entry DOI: 10.2210/pdb4nm8/pdb
• Related: 4NM4
• EMDB information: 5793 5794
• Descriptor: Hemagglutinin HA1 Chain, Hemagglutinin HA2 Chain, Antibody CR8043, Light Chain, ... (6 entities in total)
• Functional Keywords: viral fusion protein, immunoglobulin, virus attachment and entry, immune recognition, viral protein-immune system complex, immunoglobulin', viral protein/immune system
• Biological source: Influenza A virus (strain A/Hong Kong/1/1968 H3N2); More
• Total number of polymer chains: 12
• Total formula weight: 318376.41

Authors

Lee, P.S.,Wilson, I.A. (deposition date: 2013-11-14, release date: 2013-12-25, Last modification date: 2024-11-27)

Primary citation

Friesen, R.H.,Lee, P.S.,Stoop, E.J.,Hoffman, R.M.,Ekiert, D.C.,Bhabha, G.,Yu, W.,Juraszek, J.,Koudstaal, W.,Jongeneelen, M.,Korse, H.J.,Ophorst, C.,Brinkman-van der Linden, E.C.,Throsby, M.,Kwakkenbos, M.J.,Bakker, A.Q.,Beaumont, T.,Spits, H.,Kwaks, T.,Vogels, R.,Ward, A.B.,Goudsmit, J.,Wilson, I.A.
A common solution to group 2 influenza virus neutralization.
Proc.Natl.Acad.Sci.USA, 111:445-450, 2014

PubMed Abstract: The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.

PubMed: 24335589
DOI: 10.1073/pnas.1319058110

Experimental method

X-RAY DIFFRACTION (4.0041 Å)