6IUT

Crystal structure of influenza A virus H5 hemagglutinin globular head in complex with the Fab of antibody AVFluIgG01

Summary for 6IUT

• Entry DOI: 10.2210/pdb6iut/pdb
• Descriptor: AVFluIgG01 Heavy Chain, AVFluIgG01 Light Chain, Hemagglutinin, ... (6 entities in total)
• Functional Keywords: influenza virus, hpai, h5n1, neutralizing antibody, epitope, major vulnerable site, vaccine development, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 73477.59

Authors

Wang, P.,Zuo, Y.,Sun, J.,Zhang, L.,Wang, X. (deposition date: 2018-11-30, release date: 2019-01-16, Last modification date: 2023-11-22)

Primary citation

Wang, P.,Zuo, Y.,Sun, J.,Zuo, T.,Zhang, S.,Guo, S.,Shi, X.,Liang, M.,Zhou, P.,Zhang, L.,Wang, X.
Structural and functional definition of a vulnerable site on the hemagglutinin of highly pathogenic avian influenza A virus H5N1.
J. Biol. Chem., 294:4290-4303, 2019

PubMed Abstract: Most neutralizing antibodies against highly pathogenic avian influenza A virus H5N1 recognize the receptor-binding site (RBS) on the globular head domain and the stem of H5N1 hemagglutinin (HA). Through comprehensive analysis of multiple human protective antibodies, we previously identified four vulnerable sites (VS1-VS4) on the globular head domain. Among them, the VS1, occupying the opposite side of the RBS on the same HA, was defined by the epitope of antibody 65C6. In this study, we report the crystal structures of two additional human H5N1 antibodies isolated from H5N1-infected individuals, 3C11 and AVFluIgG01, bound to the head at 2.33- and 2.30-Å resolution, respectively. These two new antibody epitopes have large overlap with and extend beyond the original VS1. Site-directed mutagenesis experiments identified eight pivotal residues (Ser-126b, Lys-165, Arg-166, Ser-167, Tyr-168, Asn-169, Thr-171, and Asn-172) critical for 65C6-, 3C11-, and AVFluIgG01-binding and neutralization activities. These residues formed a unique "Y"-shaped surface on H5N1 globular head and are highly conserved among H5N1 viruses. Our results further support the existence of a vulnerable site distinct from the RBS and the stem region of H5N1 HA, and future design of immunogens should take this particular site into consideration.

PubMed: 30737282
DOI: 10.1074/jbc.RA118.007008

Experimental method

X-RAY DIFFRACTION (2.3 Å)