Laboratorio de Integración de Señales Celulares, IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.
Laboratorio de Integración de Señales Celulares, IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina.
Biochem Biophys Res Commun. 2021 Sep 10;569:154-160. doi: 10.1016/j.bbrc.2021.06.100. Epub 2021 Jul 2.
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.
新型冠状病毒 2 号核衣壳蛋白（N 蛋白）结合多种细胞宿主蛋白，包括已被充分研究的调节蛋白 14-3-3γ。然而，这种相互作用的生物学功能尚未完全了解。我们分析了约 90000 个新型冠状病毒 2 号 N 蛋白序列的变异性，特别是其无序区域结合 14-3-3 蛋白的结合基序的突变。我们研究了这些突变如何影响与 14-3-3γ 的结合能，发现对预测与 14-3-3γ 的相互作用产生积极影响的突变是传播最成功的，在系统发育树中患病率最高。虽然 14-3-3 结合位点内的大多数残基高度保守，但仍发现了一些补偿性突变以维持 N-14-3-3γ 的相互作用能，包括目前关注和感兴趣的变异株的一半。我们的研究结果表明，N 蛋白与 14-3-3γ 的结合对病毒有益，因此靶向这种病毒-宿主蛋白-蛋白相互作用似乎是一种有吸引力的探索抗病毒策略的方法。
