tetano
Editor, Senior Moderator
Cell Biosci
. 2021 Jul 22;11(1):140.
doi: 10.1186/s13578-021-00644-y.
Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV-2 replication
Yiling Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Kuijie Tong[SUP] #[/SUP][SUP] 1 [/SUP], Roubin Yao[SUP] #[/SUP][SUP] 1 [/SUP], Yuanze Zhou[SUP] 2 [/SUP], Hanwen Lin[SUP] 1 [/SUP], Liubing Du[SUP] 1 [/SUP], Yunyun Jin[SUP] 1 [/SUP], Liu Cao[SUP] 1 [/SUP], Jingquan Tan[SUP] 2 [/SUP], Xing-Ding Zhang[SUP] 1 [/SUP], Deyin Guo[SUP] 1 [/SUP], Ji-An Pan[SUP] 3 [/SUP], Xiaoxue Peng[SUP] 4 [/SUP]
Affiliations
Abstract
Background: Analysis of viral protein-protein interactions is an essential step to uncover the viral protein functions and the molecular mechanism for the assembly of a viral protein complex. We employed a mammalian two-hybrid system to screen all the viral proteins of SARS-CoV-2 for the protein-protein interactions.
Results: Our study detected 48 interactions, 14 of which were firstly reported here. Unlike Nsp1 of SARS-CoV, Nsp1 of SARS-CoV-2 has the most interacting partners among all the viral proteins and likely functions as a hub for the viral proteins. Five self-interactions were confirmed, and five interactions, Nsp1/Nsp3.1, Nsp3.1/N, Nsp3.2/Nsp12, Nsp10/Nsp14, and Nsp10/Nsp16, were determined to be positive bidirectionally. Using the replicon reporter system of SARS-CoV-2, we screened all viral Nsps for their impacts on the viral replication and revealed Nsp3.1, the N-terminus of Nsp3, significantly inhibited the replicon reporter gene expression. We found Nsp3 interacted with N through its acidic region at N-terminus, while N interacted with Nsp3 through its NTD, which is rich in the basic amino acids. Furthermore, using purified truncated N and Nsp3 proteins, we determined the direct interactions between Nsp3 and N protein.
Conclusions: Our findings provided a basis for understanding the functions of coronavirus proteins and supported the potential of interactions as the target for antiviral drug development.
Keywords: Interaction map; N; Nsp3; Replication; SARS-CoV-2.
. 2021 Jul 22;11(1):140.
doi: 10.1186/s13578-021-00644-y.
Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV-2 replication
Yiling Jiang[SUP] #[/SUP][SUP] 1 [/SUP], Kuijie Tong[SUP] #[/SUP][SUP] 1 [/SUP], Roubin Yao[SUP] #[/SUP][SUP] 1 [/SUP], Yuanze Zhou[SUP] 2 [/SUP], Hanwen Lin[SUP] 1 [/SUP], Liubing Du[SUP] 1 [/SUP], Yunyun Jin[SUP] 1 [/SUP], Liu Cao[SUP] 1 [/SUP], Jingquan Tan[SUP] 2 [/SUP], Xing-Ding Zhang[SUP] 1 [/SUP], Deyin Guo[SUP] 1 [/SUP], Ji-An Pan[SUP] 3 [/SUP], Xiaoxue Peng[SUP] 4 [/SUP]
Affiliations
- PMID: 34294141
- DOI: 10.1186/s13578-021-00644-y
Abstract
Background: Analysis of viral protein-protein interactions is an essential step to uncover the viral protein functions and the molecular mechanism for the assembly of a viral protein complex. We employed a mammalian two-hybrid system to screen all the viral proteins of SARS-CoV-2 for the protein-protein interactions.
Results: Our study detected 48 interactions, 14 of which were firstly reported here. Unlike Nsp1 of SARS-CoV, Nsp1 of SARS-CoV-2 has the most interacting partners among all the viral proteins and likely functions as a hub for the viral proteins. Five self-interactions were confirmed, and five interactions, Nsp1/Nsp3.1, Nsp3.1/N, Nsp3.2/Nsp12, Nsp10/Nsp14, and Nsp10/Nsp16, were determined to be positive bidirectionally. Using the replicon reporter system of SARS-CoV-2, we screened all viral Nsps for their impacts on the viral replication and revealed Nsp3.1, the N-terminus of Nsp3, significantly inhibited the replicon reporter gene expression. We found Nsp3 interacted with N through its acidic region at N-terminus, while N interacted with Nsp3 through its NTD, which is rich in the basic amino acids. Furthermore, using purified truncated N and Nsp3 proteins, we determined the direct interactions between Nsp3 and N protein.
Conclusions: Our findings provided a basis for understanding the functions of coronavirus proteins and supported the potential of interactions as the target for antiviral drug development.
Keywords: Interaction map; N; Nsp3; Replication; SARS-CoV-2.