MORC3 Is a Target of the Influenza A Viral Protein NS1.
MORC3 Is a Target of the Influenza A Viral Protein NS1.
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DOI：
10.1016/j.str.2019.03.015
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发表时间：
2019-06
期刊：
影响因子：
5.7
通讯作者：
Yi Zhang;Jaewoo Ahn;K. Green;K. R. Vann;Joshua C. Black;C. Brooke;T. Kutateladze
中科院分区：
文献类型：
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作者：
Yi Zhang;Jaewoo Ahn;K. Green;K. R. Vann;Joshua C. Black;C. Brooke;T. Kutateladze
Microrchidia 3（MORC 3）是一种与多种自身免疫性疾病相关的人类ATP酶，其特征在于是甲型流感病毒的负调节因子和正调节因子。在这里，我们报告说，CW域的MORC 3（MORC 3-CW）是由流感病毒H3 N2蛋白NS 1的C-末端尾部的目标。MORC 3-CW：NS 1复合物的晶体结构表明，NS 1在CW中占据了通常由MORC 3-CW的生理配体组蛋白H3占据的相同结合位点。MORC 3-CW与H3和NS 1肽以及与相邻的催化ATP酶结构域的可比结合亲和力表明，病毒蛋白可以与宿主组蛋白竞争与CW的结合，释放MORC 3自身抑制并激活MORC 3的催化功能。我们的结构、生化和细胞分析表明，MORC 3可能影响流感病毒的感染性，因此在细胞免疫应答中起作用。
Microrchidia 3 (MORC3), a human ATPase linked to several autoimmune disorders, has been characterized both as a negative and positive regulator of influenza A virus. Here, we report that the CW domain of MORC3 (MORC3-CW) is targeted by the C-terminal tail of the influenza H3N2 protein NS1. The crystal structure of the MORC3-CW:NS1 complex shows that NS1 occupies the same binding site in CW that is normally occupied by histone H3, a physiological ligand of MORC3-CW. Comparable binding affinities of MORC3-CW to H3 and NS1 peptides and to the adjacent catalytic ATPase domain suggest that the viral protein can compete with the host histone for the association with CW, releasing MORC3 autoinhibition and activating the catalytic function of MORC3. Our structural, biochemical, and cellular analyses suggest that MORC3 might affect the infectivity of influenza virus and therefore has a role in cell immune response.