Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES.
Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES.
复制标题
DOI：
10.1074/jbc.m115.700542
复制
发表时间：
2016-03-04
期刊：
影响因子：
--
通讯作者：
Hsu CH
中科院分区：
文献类型：
--
作者：
Cho CC;Lin MH;Chuang CY;Hsu CH
新出现的中东呼吸综合征冠状病毒（MERS-CoV）编码非结构蛋白3的保守大域。然而，宏观结构域的精确生化功能和结构尚不清楚。利用差示扫描荧光法和等温滴定量热法，我们表征了MERS-CoV大结构域是一个比其他cov大结构域更有效的二磷酸腺苷(ADP)-核糖结合模块。此外，在1.43-Å分辨率下测定了MERS-CoV巨域与adp核糖复合物的晶体结构。对MERS-CoV和其他人类冠状病毒宏结构域的比较发现，α1螺旋结构的差异改变了保守的Asp-20与adp -核糖的相互作用方式，这可能解释了MERS-CoV宏结构域与adp -核糖的有效结合。该研究为进一步评估MERS-CoV宏结构域通过adp -核糖结合在宿主反应中的作用提供了结构和生物物理基础，同时也为药物设计提供了潜在的靶点。
The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other CoVs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human CoVs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.