Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus
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.
Authors
- Jiayu Guan
- Jingjing Guo (ORCID: https://orcid.org/0000-0002-4632-4364)
- Guoxiang Mo
- Xiaoxia Li (ORCID: https://orcid.org/0000-0003-3972-9715)
- Shuijun Zhang (ORCID: https://orcid.org/0000-0002-9875-1501)
- Mo Yang (ORCID: https://orcid.org/0000-0002-3863-8187)
- Ying Xu (ORCID: https://orcid.org/0000-0002-1028-4639)
- Ke Ma (ORCID: https://orcid.org/0000-0003-1436-3673)
- Rong Chen (ORCID: https://orcid.org/0000-0002-2852-7221)
- Zehou Li (ORCID: https://orcid.org/0009-0007-1653-2801)
- Yuan Yuan
- Jing Chen (ORCID: https://orcid.org/0000-0001-5216-3061)
- Peng Zhou (ORCID: https://orcid.org/0000-0001-5681-9937)
- Ran Xu
- Zheng‐Li Shi (ORCID: https://orcid.org/0000-0001-8089-163X)
- Li Yang (ORCID: https://orcid.org/0000-0001-6829-8278)
- Meihua Wang (ORCID: https://orcid.org/0000-0002-8860-3329)
- Bo Shu (ORCID: https://orcid.org/0000-0002-4408-2971)
- Weiwei Ji (ORCID: https://orcid.org/0000-0001-5567-0739)
- Minjie Ren
- Zhengrong Zhou
- Jiayu Wei
Institutions
- Nanjing Agricultural University (CN)
- Anhui University (CN)
- Chinese Academy of Sciences (CN)
- Jiangsu Academy of Agricultural Sciences (CN)
- Guangzhou Experimental Station (CN)
- Wuhan Institute of Virology (CN)
- Macao Polytechnic University (MO)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1371/journal.ppat.1012695
- Citations
- 5
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.41
Funders
- Jiangsu Agricultural Science and Technology Innovation Fund
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Fundamental Research Funds for the Central Universities
- Basic and Applied Basic Research Foundation of Guangdong Province