School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Centre for Inflammation, School of Life Sciences, Faculty of Science, Centenary Institute and the University of Technology Sydney, Sydney, NSW, Australia.
Arch Microbiol. 2024 Feb 9;206(3):94. doi: 10.1007/s00203-024-03832-9.
One of the mechanisms viruses use in hijacking host cellular machinery is mimicking Short Linear Motifs (SLiMs) in host proteins to maintain their life cycle inside host cells. In the face of the escalating volume of virus-host protein-protein interactions (vhPPIs) documented in databases; the accurate prediction of molecular mimicry remains a formidable challenge due to the inherent degeneracy of SLiMs. Consequently, there is a pressing need for computational methodologies to predict new instances of viral mimicry. Our present study introduces a DMI-de-novo pipeline, revealing that vhPPIs catalogued in the VirHostNet3.0 database effectively capture domain-motif interactions (DMIs). Notably, both affinity purification coupled mass spectrometry and yeast two-hybrid assays emerged as good approaches for delineating DMIs. Furthermore, we have identified new vhPPIs mediated by SLiMs across different viruses. Importantly, the de-novo prediction strategy facilitated the recognition of several potential mimicry candidates implicated in the subversion of host cellular proteins. The insights gleaned from this research not only enhance our comprehension of the mechanisms by which viruses co-opt host cellular machinery but also pave the way for the development of novel therapeutic interventions.
病毒在劫持宿主细胞机制的过程中，会模仿宿主蛋白中的短线性基序 (SLiMs)，以维持其在宿主细胞内的生命周期。面对数据库中记录的不断增加的病毒-宿主蛋白-蛋白相互作用 (vhPPIs)，由于 SLiMs 的固有简并性，准确预测分子模拟仍然是一项艰巨的挑战。因此，迫切需要计算方法来预测新的病毒模拟实例。我们目前的研究引入了一种 DMI-de-novo 管道，表明在 VirHostNet3.0 数据库中编目的 vhPPIs 有效地捕获了结构域-基序相互作用 (DMIs)。值得注意的是，亲和纯化结合质谱和酵母双杂交测定都被证明是描绘 DMIs 的好方法。此外，我们已经鉴定了不同病毒介导的新的 vhPPIs。重要的是，从头预测策略有助于识别几个潜在的模拟候选物，这些候选物涉及宿主细胞蛋白的颠覆。这项研究的见解不仅增强了我们对病毒利用宿主细胞机制的理解，也为开发新的治疗干预措施铺平了道路。
