Structure of Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Has Implications for Coronavirus nsp1 Function and Evolution
Structure of Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Has Implications for Coronavirus nsp1 Function and Evolution
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DOI：
10.1128/jvi.03163-12
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发表时间：
2013-03-01
影响因子：
5.4
通讯作者：
Jansson, Anna M.
中科院分区：
文献类型：
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作者：
Jansson, Anna M.
冠状病毒 nsp1 已被证明可诱导宿主基因表达抑制并干扰宿主免疫反应。然而，目前尚不清楚其机制。关于冠状病毒 nsp1 的唯一可用结构信息是来自 β 冠状病毒属的严重急性呼吸综合征冠状病毒 (SARS-CoV) 的 nsp1 N 末端结构域的核磁共振 (NMR) 结构。在这里，我们展示了来自α冠状病毒、传染性胃肠炎病毒（TGEV）nsp1的第一个nsp1结构。它显示出六链 β 桶状折叠，桶状边缘有一个长 α 螺旋，与 SARS-CoV nsp1(13-128) 共有这种折叠。与之前的推测相反，TGEV nsp1 结构表明冠状病毒 nsp1 具有共同起源，尽管缺乏序列同源性。然而，通过比较 α 和 β 冠状病毒之间的表面静电、形状和氨基酸保守性，我们推测这两个属中 nsp1 诱导的宿主基因表达抑制机制可能不同。
Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune response. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmissible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded beta-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp1(13-128). Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.