tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2021 Jul 2;569:154-160.
doi: 10.1016/j.bbrc.2021.06.100. Online ahead of print.
Analysis of SARS-CoV-2 nucleocapsid phosphoprotein N variations in the binding site to human 14-3-3 proteins
Samanta Del Veliz[SUP] 1 [/SUP], Lautaro Rivera[SUP] 1 [/SUP], Diego M Bustos[SUP] 2 [/SUP], Marina Uhart[SUP] 3 [/SUP]
Affiliations
Abstract
The SARS-CoV-2 N protein binds several cell host proteins including 14-3-3γ, a well-characterized regulatory protein. However, the biological function of this interaction is not completely understood. We analyzed the variability of ∼90 000 sequences of the SARS-CoV-2 N protein, particularly, its mutations in disordered regions containing binding motifs for 14-3-3 proteins. We studied how these mutations affect the binding energy to 14-3-3γ and found that changes positively affecting the predicted interaction with 14-3-3γ are the most successfully spread, with the highest prevalence in the phylogenetic tree. Although most residues are highly conserved within the 14-3-3 binding site, compensatory mutations to maintain the interaction energy of N-14-3-3γ were found, including half of the current variants of concern and interest. Our results suggest that binding of N to 14-3-3γ is beneficial for the virus, thus targeting this viral-host protein-protein interaction seems an attractive approach to explore antiviral strategies.
Keywords: 14-3-3; Coronavirus; Interaction; N protein; SARS-CoV-2; Viral success.
. 2021 Jul 2;569:154-160.
doi: 10.1016/j.bbrc.2021.06.100. Online ahead of print.
Analysis of SARS-CoV-2 nucleocapsid phosphoprotein N variations in the binding site to human 14-3-3 proteins
Samanta Del Veliz[SUP] 1 [/SUP], Lautaro Rivera[SUP] 1 [/SUP], Diego M Bustos[SUP] 2 [/SUP], Marina Uhart[SUP] 3 [/SUP]
Affiliations
- PMID: 34246830
- DOI: 10.1016/j.bbrc.2021.06.100
Abstract
The SARS-CoV-2 N protein binds several cell host proteins including 14-3-3γ, a well-characterized regulatory protein. However, the biological function of this interaction is not completely understood. We analyzed the variability of ∼90 000 sequences of the SARS-CoV-2 N protein, particularly, its mutations in disordered regions containing binding motifs for 14-3-3 proteins. We studied how these mutations affect the binding energy to 14-3-3γ and found that changes positively affecting the predicted interaction with 14-3-3γ are the most successfully spread, with the highest prevalence in the phylogenetic tree. Although most residues are highly conserved within the 14-3-3 binding site, compensatory mutations to maintain the interaction energy of N-14-3-3γ were found, including half of the current variants of concern and interest. Our results suggest that binding of N to 14-3-3γ is beneficial for the virus, thus targeting this viral-host protein-protein interaction seems an attractive approach to explore antiviral strategies.
Keywords: 14-3-3; Coronavirus; Interaction; N protein; SARS-CoV-2; Viral success.