1] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, PR China [2] Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [3].
Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
Nat Commun. 2014 May 23;5:3952. doi: 10.1038/ncomms4952.
Pathogens can interfere with vital biological processes of their host by mimicking host proteins. The NS1 protein of the influenza A H3N2 subtype possesses a histone H3K4-like sequence at its carboxyl terminus and has been reported to use this mimic to hijack host proteins. However, this mimic lacks a free N-terminus that is essential for binding to many known H3K4 readers. Here we show that the double chromodomains of CHD1 adopt an 'open pocket' to interact with the free N-terminal amine of H3K4, and the open pocket permits the NS1 mimic to bind in a distinct conformation. We also explored the possibility that NS1 hijacks other cellular proteins and found that the NS1 mimic has access to only a subset of chromatin-associated factors, such as WDR5. Moreover, methylation of the NS1 mimic can not be reversed by the H3K4 demethylase LSD1. Overall, we thus conclude that the NS1 mimic is an imperfect histone mimic.
病原体可以通过模拟宿主蛋白来干扰宿主的重要生物过程。甲型 H3N2 亚型流感的 NS1 蛋白在其羧基末端具有组蛋白 H3K4 样序列，据报道，它利用这种模拟物来劫持宿主蛋白。然而，这种模拟物缺乏与许多已知的 H3K4 读取器结合所必需的游离 N 端。在这里，我们表明 CHD1 的双 chromodomains 采用“开放口袋”与 H3K4 的游离 N 端胺相互作用，并且开放口袋允许 NS1 模拟物以独特的构象结合。我们还探讨了 NS1 是否劫持其他细胞蛋白的可能性，发现 NS1 模拟物只能与一小部分与染色质相关的因子（如 WDR5）相互作用。此外，NS1 模拟物的甲基化不能被 H3K4 去甲基酶 LSD1 逆转。总的来说，我们得出结论，NS1 模拟物是一种不完美的组蛋白模拟物。
