5UL6

The molecular mechanisms by which NS1 of the 1918 Spanish influenza A virus hijack host protein-protein interactions

5UL6 の概要

• エントリーDOI: 10.2210/pdb5ul6/pdb
• 分子名称: Adapter molecule crk, Proline-rich motif of nonstructural protein 1 of influenza a virus (3 entities in total)
• 機能のキーワード: sh3, crkii, nonstructural protein 1, influenza a virus, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : P46108
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8565.69

構造登録者

Shen, Q.,Zeng, D.,Zhao, B.,Li, P.,Cho, J.H. (登録日: 2017-01-24, 公開日: 2017-08-09, 最終更新日: 2024-11-13)

主引用文献

Shen, Q.,Zeng, D.,Zhao, B.,Bhatt, V.S.,Li, P.,Cho, J.H.
The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.
ACS Chem. Biol., 12:1199-1203, 2017

PubMed Abstract: The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster k and 3300-fold lower K compared to those for the CrkII-JNK1 interaction. These results provide molecular insight into the mechanism by which 1918 IAV NS1 hijacks CrkII and disrupts its interactions with critical cellular signaling proteins.

PubMed: 28368102
DOI: 10.1021/acschembio.7b00168

実験手法

X-RAY DIFFRACTION (1.45 Å)