3FKU

Crystal structure of influenza hemagglutinin (H5) in complex with a broadly neutralizing antibody F10

Summary for 3FKU

• Entry DOI: 10.2210/pdb3fku/pdb
• Related: 2FK0 2GHW 2IBX
• Descriptor: Hemagglutinin, Hemagglutinin HA2 chain, Neutralizing antibody F10, ... (5 entities in total)
• Functional Keywords: influenza, hemagglutinin, neutralizing antibody, scfv, h5, f10, cell membrane, envelope protein, fusion protein, membrane, transmembrane, virion, cleavage on pair of basic residues, glycoprotein, lipoprotein, palmitate, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/Viet Nam/1203/2004(H5N1)); More
• Cellular location: Virion membrane; Single-pass type I membrane protein (Potential): A8UDR4
• Total number of polymer chains: 18
• Total formula weight: 538427.88

Authors

Hwang, W.C.,Santelli, E.,Stec, B.,Wei, G.,Cadwell, G.,Bankston, L.A.,Sui, J.,Perez, S.,Aird, D.,Chen, L.M.,Ali, M.,Murakami, A.,Yammanuru, A.,Han, T.,Cox, N.,Donis, R.O.,Liddington, R.C.,Marasco, W.A. (deposition date: 2008-12-17, release date: 2009-02-24, Last modification date: 2024-12-25)

Primary citation

Sui, J.,Hwang, W.C.,Perez, S.,Wei, G.,Aird, D.,Chen, L.M.,Santelli, E.,Stec, B.,Cadwell, G.,Ali, M.,Wan, H.,Murakami, A.,Yammanuru, A.,Han, T.,Cox, N.J.,Bankston, L.A.,Donis, R.O.,Liddington, R.C.,Marasco, W.A.
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses.
Nat.Struct.Mol.Biol., 16:265-273, 2009

PubMed Abstract: Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

PubMed: 19234466
DOI: 10.1038/nsmb.1566

Experimental method

X-RAY DIFFRACTION (3.2 Å)