9MQW
Crystal structure of influenza virus N2 neuraminidase from A/Singapore/INFIMH-16-0019/2016 (H3N2)
Summary for 9MQW
| Entry DOI | 10.2210/pdb9mqw/pdb |
| Related | 9MQV |
| Descriptor | Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | hydrolase, immune system, influenza virus, neuraminidase, neutralization, substrate mimicry, viral protein, viral protein-hydrolase complex, viral protein/hydrolase |
| Biological source | Influenza A virus |
| Total number of polymer chains | 1 |
| Total formula weight | 48106.54 |
| Authors | |
| Primary citation | Zhu, X.,Khalil, A.M.,Piepenbrink, M.S.,Yu, W.,Ma, Y.,Martinez-Sobrido, L.,Wilson, I.A.,Kobie, J.J. Structure and function of a cross-neutralizing influenza neuraminidase antibody that accommodates recent N2 NA Asn245 glycosylation. Biorxiv, 2025 Cited by PubMed Abstract: Monoclonal antibodies (mAbs) that recognize and inhibit a diverse range of influenza viruses, although relatively rare, have been isolated following infection or vaccination. Study of their ontology and mechanisms of action informs universal vaccine and therapeutic development. We have previously described a potent and broad neuraminidase (NA)-neutralizing human mAb, 1122A11, that neutralizes a wide range of H3N2 viruses. Here, further characterization of 1122A11 reveals reactivity to cross-group influenza A virus NAs, including group-1 N1 and N8, and group-2 N2 and N3 NAs. Recent H3N2 viruses have acquired Asn245 glycosylation on the active site rim. Crystal structures of an N2 NA from A/Singapore/INFIMH-16-0019/2016 (H3N2) at 2.3 Å (apo) and 2.2 Å (Fab bound) resolution showed that 1122A11 binding causes local changes to the periphery of NA active site to accommodate the glycan. The CDRH3 of 1122A11 inserts into the active site and mimics the substrate sialic acid. We then determined that the ability of 1122A11 to protect from lethal challenge in mice is not dependent on Fc-effector function. These results highlight the therapeutic potential of 1122A11 as a broad protective anti-viral and reinforce pursuit of immunogen development of NA antibodies toward achieving more universal influenza protection. PubMed: 40631320DOI: 10.1101/2025.06.30.662356 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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