9GQT

influenza neuraminidase hybrid N1/09

9GQT の概要

• エントリーDOI: 10.2210/pdb9gqt/pdb
• 分子名称: Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: influenza neuraminidase hybrid expression, viral protein
• 由来する生物種: unidentified influenza virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112970.93

構造登録者

Bowden, T.A.,Paesen, G.C. (登録日: 2024-09-09, 公開日: 2025-06-11, 最終更新日: 2025-09-24)

主引用文献

Rijal, P.,Wei, L.,Paesen, G.C.,Stuart, D.I.,Haworth, M.,Huang, K.A.,Bowden, T.A.,Townsend, A.R.M.
Structure-guided loop grafting improves expression and stability of influenza neuraminidase for vaccine development.
Elife, 14:-, 2025

PubMed Abstract: Influenza virus neuraminidase (NA) is a crucial target for protective antibodies, yet the development of recombinant NA protein as a vaccine has been held back by instability and variable expression. We have taken a pragmatic approach to improving expression and stability of NA by grafting antigenic surface loops from low-expressing NA proteins onto the scaffold of high-expressing counterparts. The resulting hybrid proteins retained the antigenic properties of the loop donor while benefiting from the high-yield expression, stability, and tetrameric structure of the loop recipient. These hybrid proteins were recognised by a broad set of human monoclonal antibodies elicited by influenza infection or vaccination, with X-ray structures validating the accurate structural conformation of the grafted loops and the enzymatic cavity. Immunisation of mice with NA hybrids induced inhibitory antibodies to the loop donor and protected against lethal influenza challenge. This pragmatic technique offers a robust solution for improving the expression and stability of influenza NA proteins for vaccine development.

PubMed: 40924000
DOI: 10.7554/eLife.105317

実験手法

X-RAY DIFFRACTION (1.94 Å)