6PZW

CryoEM derived model of NA-22 Fab in complex with N9 Shanghai2

Summary for 6PZW

• Entry DOI: 10.2210/pdb6pzw/pdb
• EMDB information: 20538 20540 20541
• Descriptor: Neuraminidase, NA-22 fragment antigen binding light chain, NA-22 fragment antigen binding heavy chain, ... (6 entities in total)
• Functional Keywords: neuraminidase, na, sh2, n9shanghai, n9sh2, antibody, fab, na-22, influenza, viral protein-immune system complex, h7n9, viral protein/immune system
• Biological source: Influenza A virus (A/environment/Shanghai/S1439/2013(H7N9)); More
• Total number of polymer chains: 12
• Total formula weight: 390050.73

Authors

Ward, A.B.,Turner, H.L.,Zhu, X. (deposition date: 2019-08-01, release date: 2019-12-04, Last modification date: 2024-10-09)

Primary citation

Zhu, X.,Turner, H.L.,Lang, S.,McBride, R.,Bangaru, S.,Gilchuk, I.M.,Yu, W.,Paulson, J.C.,Crowe Jr., J.E.,Ward, A.B.,Wilson, I.A.
Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies.
Cell Host Microbe, 26:729-, 2019

PubMed Abstract: Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host protection. However, our understanding of the nature and range of target epitopes is limited because of a lack of human antibody structures with influenza neuraminidase. Here, we describe crystal and cryogenic electron microscopy (cryo-EM) structures of NAs from human-infecting avian H7N9 viruses in complex with five human anti-N9 antibodies, systematically defining several antigenic sites and antibody epitope footprints. These antibodies either fully or partially block the NA active site or bind to epitopes distant from the active site while still showing neuraminidase inhibition. The inhibition of antibodies to NAs was further analyzed by glycan array and solution-based NA activity assays. Together, these structural studies provide insights into protection by anti-NA antibodies and templates for the development of NA-based influenza virus vaccines and therapeutics.

PubMed: 31757767
DOI: 10.1016/j.chom.2019.10.002

Experimental method

ELECTRON MICROSCOPY (3 Å)