新型人类冠状病毒MERS-CoV及其受体CD26之间的结合的分子基础
Guangwen Lu1, Yawei Hu, Qihui Wang
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Nature
|July 9, 2013
概括
中东呼吸综合征冠状病毒 (MERS-CoV) 使用CD26 (二乙酶4) 作为其细胞受体. 结构分析揭示了MERS-CoV的尖端蛋白质.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 中东呼吸综合征冠状病毒 (MERS-CoV) 是一种高度致病性病毒.
- CD26 (二乙酶4,DPP4) 被确定为MERS-CoV. 的细胞受体.
- 了解MERS-CoV尖端蛋白和CD26相互作用对于治疗开发至关重要.
研究的目的:
- 阐明MERS-CoV尖端蛋白与其细胞受体CD26.2的相互作用的分子基础.
- 提供MERS-CoV尖端蛋白的受体结合域 (RBD) 和其与CD26.2的复合物的第一个晶体结构.
主要方法:
- 进行X射线晶体学以确定MERS-CoV RBD的结构及其与CD26.6的复合体.
- 实时表面等离子体共振测量MERS-CoV RBD和CD26.6之间的结合亲和力.
主要成果:
- 晶体结构揭示了MERS-CoV RBD-CD26相互作用的原子细节.
- 用 16.7 nM 的解离常数 (Kd) 测量结合亲和力.
- MERS-CoV RBD 具有保存的核心和可变的外部动机用于受体识别.
结论:
- 这项研究描述了MERS-CoV及其受体CD26.2之间的分子相互作用.
- 结构洞察力突出显示了冠状病毒尖端蛋白中的保留和可变区域,影响了病原和受体特异性.
- 这些发现为开发针对MERS-CoV的向抗病毒策略提供了基础.
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