8DWB

Neuraminidase from influenza virus A/Moscow/10/1999(H3N2) in complex with sialic acid

This is a non-PDB format compatible entry.

Summary for 8DWB

• Entry DOI: 10.2210/pdb8dwb/pdb
• Descriptor: Neuraminidase, alpha-D-mannopyranose-(1-3)-[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, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: neuraminidase, influenza, viral protein, hydrolase
• Biological source: Influenza A virus (A/Moscow/10/1999(H3N2))
• Total number of polymer chains: 1
• Total formula weight: 45310.08

Authors

Lei, R.,Hernandez Garcia, A. (deposition date: 2022-08-01, release date: 2022-12-21, Last modification date: 2023-10-25)

Primary citation

Lei, R.,Hernandez Garcia, A.,Tan, T.J.C.,Teo, Q.W.,Wang, Y.,Zhang, X.,Luo, S.,Nair, S.K.,Peng, J.,Wu, N.C.
Mutational fitness landscape of human influenza H3N2 neuraminidase.
Cell Rep, 42:111951-111951, 2023

PubMed Abstract: Influenza neuraminidase (NA) has received increasing attention as an effective vaccine target. However, its mutational tolerance is not well characterized. Here, the fitness effects of >6,000 mutations in human H3N2 NA are probed using deep mutational scanning. Our result shows that while its antigenic regions have high mutational tolerance, there are solvent-exposed regions with low mutational tolerance. We also find that protein stability is a major determinant of NA mutational fitness. The deep mutational scanning result correlates well with mutational fitness inferred from natural sequences using a protein language model, substantiating the relevance of our findings to the natural evolution of circulating strains. Additional analysis further suggests that human H3N2 NA is far from running out of mutations despite already evolving for >50 years. Overall, this study advances our understanding of the evolutionary potential of NA and the underlying biophysical constraints, which in turn provide insights into NA-based vaccine design.

PubMed: 36640354
DOI: 10.1016/j.celrep.2022.111951

Experimental method

X-RAY DIFFRACTION (1.602 Å)