Giri Rajanish, Kumar Deepak, Sharma Nitin, Uversky Vladimir N
School of Basic Sciences, Indian Institute of Technology Mandi Mandi, India.
Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South FloridaTampa, FL, USA; Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of SciencesSaint Petersburg, Russia.
Front Cell Infect Microbiol. 2016 Nov 4;6:144. doi: 10.3389/fcimb.2016.00144. eCollection 2016.
Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of disorder-based drugs.
在过去几十年中,蛋白质内在无序的概念已涉及不同的生物过程。最近的研究表明,内在无序蛋白质(IDP)为参与宿主细胞快速复制和免疫逃逸的病毒蛋白提供结构可塑性和功能多样性。就寨卡病毒而言,蛋白质内在无序在发病机制中的作用尚未完全了解。在本研究中,我们分析了寨卡病毒蛋白质组(MR 766株)中内在无序的普遍性。我们的分析表明,寨卡病毒多蛋白富含内在无序蛋白区域(IDPR),这一发现与先前关于IDP参与该病毒科的外壳形成和毒力的报道一致。我们在参与成熟颗粒形成和复制的衣壳、NS2B、NS3、NS4A和NS5蛋白中发现了大量IDPR。我们认为,对寨卡病毒蛋白进行以内在无序为重点的分析可能对开发基于无序的药物很重要。