7U4F

Neuraminidase from influenza virus A/Moscow/10/1999(H3N2)

7U4F の概要

• エントリーDOI: 10.2210/pdb7u4f/pdb
• 分子名称: Neuraminidase, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[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, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: neuraminidase, influenza, viral protein, hydrolase
• 由来する生物種: Influenza A virus (A/Moscow/10/1999(H3N2))
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45199.95

構造登録者

Lei, R.,Hernandez Garcia, A. (登録日: 2022-02-28, 公開日: 2022-10-19, 最終更新日: 2024-10-16)

主引用文献

Lei, R.,Tan, T.J.C.,Hernandez Garcia, A.,Wang, Y.,Diefenbacher, M.,Teo, C.,Gopan, G.,Tavakoli Dargani, Z.,Teo, Q.W.,Graham, C.S.,Brooke, C.B.,Nair, S.K.,Wu, N.C.
Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase.
Nat Commun, 13:6443-6443, 2022

PubMed Abstract: Neuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories of NA remain largely elusive. Here, we show that among 70 natural mutations that are present in the NA of a recent human H3N2 strain, >10% are deleterious for an ancestral strain. By mapping the permissive mutations using combinatorial mutagenesis and next-generation sequencing, an extensive epistatic network is revealed. Biophysical and structural analyses further demonstrate that certain epistatic interactions can be explained by non-additive stability effect, which in turn modulates membrane trafficking and enzymatic activity of NA. Additionally, our results suggest that other biophysical mechanisms also contribute to epistasis in NA evolution. Overall, these findings not only provide mechanistic insights into the evolution of human influenza NA and elucidate its sequence-structure-function relationship, but also have important implications for the development of next-generation influenza vaccines.

PubMed: 36307418
DOI: 10.1038/s41467-022-34060-8

実験手法

X-RAY DIFFRACTION (1.4 Å)