Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus

被引:0
作者
Yang, Mo [1 ]
Li, Zehou [1 ]
Chen, Jing [2 ]
Li, Yang [2 ]
Xu, Ran [3 ]
Wang, Meihua [2 ]
Xu, Ying [1 ]
Chen, Rong [4 ]
Ji, Weiwei [1 ]
Li, Xiaoxia [1 ]
Wei, Jiayu [1 ]
Zhou, Zhengrong [1 ]
Ren, Minjie [1 ]
Ma, Ke [1 ]
Guan, Jiayu [1 ]
Mo, Guoxiang [1 ]
Zhou, Peng [5 ]
Shu, Bo [2 ]
Guo, Jingjing [3 ]
Yuan, Yuan [6 ]
Shi, Zheng-Li [2 ]
Zhang, Shuijun [1 ]
机构
[1] Nanjing Agr Univ, Coll Life Sci, Nanjing, Peoples R China
[2] Chinese Acad Sci, Wuhan Inst Virol, Key Lab Virol & Biosafety, Wuhan, Peoples R China
[3] Macao Polytech Univ, Fac Appl Sci, Ctr Artificial Intelligence Driven Drug Discovery, Taipa, Macao, Peoples R China
[4] Jiangsu Acad Agr Sci, Inst Vet Med, Key Lab Vet Biol Engn & Technol, Minist Agr, Nanjing, Peoples R China
[5] Guangzhou Int Bio Isl, Guangzhou Lab, Guangzhou, Guangdong, Peoples R China
[6] Anhui Univ, Sch Life Sci, Hefei, Anhui, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
RESPIRATORY SYNDROME CORONAVIRUS; BAT; BINDING; COV; BETACORONAVIRUS; DOMAIN;
D O I
10.1371/journal.ppat.1012695
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Middle East respiratory syndrome coronavirus (MERS-CoV) and the pangolin MERS-like coronavirus MjHKU4r-CoV-1 employ dipeptidyl peptidase 4 (DPP4) as an entry receptor. MjHKU4r-CoV-1 could infect transgenic mice expressing human DPP4. To understand the mechanism of MjHKU4r-CoV-1 entry into cells, we determined the crystal structures of the receptor binding domain (RBD) of MjHKU4r-CoV-1 spike protein bound to human DPP4 (hDPP4) and Malayan pangolin DPP4 (MjDPP4), respectively. The overall hDPP4-binding mode of MjHKU4r-CoV-1 RBD is similar to that of MERS-CoV RBD. MjHKU4r-CoV-1 RBD shows higher binding affinity to hDPP4 compared to the bat MERS-like coronavirus Ty-BatCoV-HKU4. Via swapping residues between MjHKU4r-CoV-1 RBD and Ty-BatCoV-HKU4 RBD, we identified critical determinants on MjHKU4r-CoV-1 that are responsible for virus usage of hDPP4. Our study suggests that MjHKU4r-CoV-1 is more adapted to the human receptor compared to the bat HKU4 coronavirus and highlights the potential of virus emergence into the human population.
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页数:19
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