tetano
Editor, Senior Moderator
PLoS Pathog
. 2024 Nov 8;20(11):e1012695.
doi: 10.1371/journal.ppat.1012695. Online ahead of print. Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus
Mo Yang[SUP] 1 [/SUP], Zehou Li[SUP] 1 [/SUP], Jing Chen[SUP] 2 [/SUP], Yang Li[SUP] 2 [/SUP], Ran Xu[SUP] 3 [/SUP], Meihua Wang[SUP] 2 [/SUP], Ying Xu[SUP] 1 [/SUP], Rong Chen[SUP] 4 [/SUP], Weiwei Ji[SUP] 1 [/SUP], Xiaoxia Li[SUP] 1 [/SUP], Jiayu Wei[SUP] 1 [/SUP], Zhengrong Zhou[SUP] 1 [/SUP], Minjie Ren[SUP] 1 [/SUP], Ke Ma[SUP] 1 [/SUP], Jiayu Guan[SUP] 1 [/SUP], Guoxiang Mo[SUP] 1 [/SUP], Peng Zhou[SUP] 5 [/SUP], Bo Shu[SUP] 2 [/SUP], Jingjing Guo[SUP] 3 [/SUP], Yuan Yuan[SUP] 6 [/SUP], Zheng-Li Shi[SUP] 2 [/SUP], Shuijun Zhang[SUP] 1 [/SUP]
Affiliations
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.
. 2024 Nov 8;20(11):e1012695.
doi: 10.1371/journal.ppat.1012695. Online ahead of print. Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus
Mo Yang[SUP] 1 [/SUP], Zehou Li[SUP] 1 [/SUP], Jing Chen[SUP] 2 [/SUP], Yang Li[SUP] 2 [/SUP], Ran Xu[SUP] 3 [/SUP], Meihua Wang[SUP] 2 [/SUP], Ying Xu[SUP] 1 [/SUP], Rong Chen[SUP] 4 [/SUP], Weiwei Ji[SUP] 1 [/SUP], Xiaoxia Li[SUP] 1 [/SUP], Jiayu Wei[SUP] 1 [/SUP], Zhengrong Zhou[SUP] 1 [/SUP], Minjie Ren[SUP] 1 [/SUP], Ke Ma[SUP] 1 [/SUP], Jiayu Guan[SUP] 1 [/SUP], Guoxiang Mo[SUP] 1 [/SUP], Peng Zhou[SUP] 5 [/SUP], Bo Shu[SUP] 2 [/SUP], Jingjing Guo[SUP] 3 [/SUP], Yuan Yuan[SUP] 6 [/SUP], Zheng-Li Shi[SUP] 2 [/SUP], Shuijun Zhang[SUP] 1 [/SUP]
Affiliations
- PMID: 39514585
- DOI: 10.1371/journal.ppat.1012695
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.