8TWP

Influenza A virus (A/Aichi/2/1968(H3N2) nucleoprotein mutant - 2-7 deleted, R416A

8TWP の概要

• エントリーDOI: 10.2210/pdb8twp/pdb
• 分子名称: Nucleoprotein (1 entity in total)
• 機能のキーワード: nucleoprotein, influenza, viral protein
• 由来する生物種: Influenza A virus (A/Aichi/2/1968(H3N2))
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 169920.40

構造登録者

Yoon, J.,Zhang, Y.M.,Grant, R.A.,Shoulders, M.D. (登録日: 2023-08-21, 公開日: 2024-07-03, 最終更新日: 2024-07-10)

主引用文献

Yoon, J.,Zhang, Y.M.,Her, C.,Grant, R.A.,Ponomarenko, A.I.,Ackermann, B.E.,Hui, T.,Lin, Y.S.,Debelouchina, G.T.,Shoulders, M.D.
The immune-evasive proline-283 substitution in influenza nucleoprotein increases aggregation propensity without altering the native structure.
Sci Adv, 10:eadl6144-eadl6144, 2024

PubMed Abstract: Nucleoprotein (NP) is a key structural protein of influenza ribonucleoprotein complexes and is central to viral RNA packing and trafficking. NP also determines the sensitivity of influenza to myxovirus resistance protein 1 (MxA), an innate immunity factor that restricts influenza replication. A few critical MxA-resistant mutations have been identified in NP, including the highly conserved proline-283 substitution. This essential proline-283 substitution impairs influenza growth, a fitness defect that becomes particularly prominent at febrile temperature (39°C) when host chaperones are depleted. Here, we biophysically characterize proline-283 NP and serine-283 NP to test whether the fitness defect is caused by the proline-283 substitution introducing folding defects. We show that the proline-283 substitution changes the folding pathway of NP, making NP more aggregation prone during folding, but does not alter the native structure of the protein. These findings suggest that influenza has evolved to hijack host chaperones to promote the folding of otherwise biophysically incompetent viral proteins that enable innate immune system escape.

PubMed: 38640233
DOI: 10.1126/sciadv.adl6144

実験手法

X-RAY DIFFRACTION (2.9 Å)