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人类DPP4受体识别的结构基础由松鼠的MERS类冠状病毒识别

Mo Yang¹, Zehou Li¹, Jing Chen²

¹College of Life Sciences, Nanjing Agricultural University, Nanjing, China.

|November 8, 2024

概括

长冠状病毒MjHKU4r-CoV-1使用人类二基酶4 (DPP4) 进入细胞. 这种病毒比蝙蝠冠状病毒更适应人类的DPP4,这表明人类的潜在出现.

科学领域:

病毒学病毒学
结构生物学结构生物学
分子相互作用分子相互作用

背景情况:

中东呼吸系统综合征冠状病毒 (MERS-CoV) 和松鼠MERS类冠状病毒MjHKU4r-CoV-1利用二二酶4 (DPP4) 作为它们的细胞进入受体.
MjHKU4r-CoV-1已在表达人类DPP4的转基因小鼠中显示出感染性.

研究的目的:

通过确定其与DPP4相互作用的结构基础来阐明MjHKU4r-CoV-1细胞进入的机制.
为了比较MjHKU4r-CoV-1与其他类似MERS的冠状病毒的结合亲和力和决定因素.

主要方法:

确定了MjHKU4r-CoV-1受体结合域 (RBD) 与人类DPP4 (hDPP4) 和马来亚松鼠DPP4 (MjDPP4) 复合的晶体结构.
进行了RBD-DPP4结合方式和亲缘关系的比较分析.
利用MjHKU4r-CoV-1 RBD和Ty-BatCoV-HKU4 RBD之间的残留物交换实验来确定关键的结合决定因素.

主要成果:

MjHKU4r-CoV-1 RBD与hDPP4的结合方式在结构上与MERS-CoV RBD的结合方式相似.
与蝙蝠冠状病毒Ty-BatCoV-HKU4相比,MjHKU4r-CoV-1 RBD对hDPP4具有更高的结合亲和力.
通过残留物交换确定了负责MjHKU4r-CoV-1与hDPP4相互作用的关键残留物.

结论:

与蝙蝠HKU4冠状病毒相比,MjHKU4r-CoV-1表现出对人类DPP4受体的增强适应性.
这些发现突出了MjHKU4r-CoV-1或类似病毒出现并感染人类人口的潜力.
结构洞察力为了解冠状病毒与宿主受体相互作用和预测动物感染潜力的基础.

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