6N6B

The complex crystal structure of neuraminidase from A/Minnesota/11/2010 with B10 antibody.

Summary for 6N6B

• Entry DOI: 10.2210/pdb6n6b/pdb
• Descriptor: Neuraminidase, B10 antibody Heavy Chain Fab, B10 antibody Light Chain Fab, ... (7 entities in total)
• Functional Keywords: neuraminidase, influenza, antibody complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/Minnesota/11/2010(H3N2)); More
• Total number of polymer chains: 3
• Total formula weight: 92820.75

Authors

Yang, H.,Stevens, J. (deposition date: 2018-11-26, release date: 2019-07-03, Last modification date: 2024-10-16)

Primary citation

Wan, H.,Gao, J.,Yang, H.,Yang, S.,Harvey, R.,Chen, Y.Q.,Zheng, N.Y.,Chang, J.,Carney, P.J.,Li, X.,Plant, E.,Jiang, L.,Couzens, L.,Wang, C.,Strohmeier, S.,Wu, W.W.,Shen, R.F.,Krammer, F.,Cipollo, J.F.,Wilson, P.C.,Stevens, J.,Wan, X.F.,Eichelberger, M.C.,Ye, Z.
The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
Nat Microbiol, 4:2216-2225, 2019

PubMed Abstract: A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.

PubMed: 31406333
DOI: 10.1038/s41564-019-0522-6

Experimental method

X-RAY DIFFRACTION (2.3 Å)