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了解基孔肯雅病毒蛋白的相互作用性——分子识别特征分析

Understanding the interactability of chikungunya virus proteins molecular recognition feature analysis.

作者信息

Singh Ankur, Kumar Ankur, Uversky Vladimir N, Giri Rajanish

机构信息

School of Basic Sciences, Indian Institute of Technology Mandi Mandi Himachal Pradesh 175005 India

Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida 12901 Bruce B. Downs Blvd. MDC07 Tampa Florida 33612 USA

出版信息

RSC Adv. 2018 Jul 31;8(48):27293-27303. doi: 10.1039/c8ra04760j. eCollection 2018 Jul 30.

Abstract

The chikungunya virus (CHIKV) is an alphavirus that has an enveloped icosahedral capsid and is transmitted by sp. mosquitos. It contains four non-structural proteins, namely nsP1, nsP2, nsP3, and nsP4, encoded at the 5' end of the genome, and five structural proteins encoded at the 3' end of the genome, including three glycosylated proteins, namely E1, E2, E3, a small 64 amino-acids glycoprotein 6K, and one non-glycosylated nucleocapsid protein C. The surface of this positive-stranded RNA alphavirus is covered with 80 trimeric glycoprotein spikes, which facilitate viral access into the host cell, with each consisting of three copies of E1-E2 heterodimers. The proper folding of p62, which is the precursor of E2, and formation of the E1-p62 heterodimers are controlled by E3, which is therefore essential for producing mature spikes on the alphavirus surface. Finally, 6K, a small 64 amino-acids glycoprotein, assists in the translocation of structural polyproteins to the endoplasmic reticulum and in the cleavage of p62 into mature structural proteins E2. The CHIKV proteins have been shown to contain variable levels of intrinsic disorder, often containing intrinsically disordered protein regions (IDPRs). IDPRs can interact with many unrelated partners, and these interactions are frequently accompanied by a transition from a disordered to ordered state. The corresponding sub-regions of IDPRs are acknowledged as molecular recognition features (MoRFs). Although the existence of IDPRs in CHIKV proteome has been analyzed, the prevalence of disorder-based protein-protein interactions ( MoRF) in this virus have not been evaluated as of yet. To fill this gap, in our study, we utilized several computational methods to identify the MoRFs regions in CHIKV proteins. These computational tools included ANCHOR, DISOPRED3, MoRFpred and MoRFchibi_web server. These analyses revealed the presence of numerous MoRF regions in all the CHIKV proteins. In future, the results of this study could be used to identify the nature of chikungunya virus pathogenesis and might be helpful in designing drugs against this virus.

摘要

基孔肯雅病毒(CHIKV)是一种甲病毒,具有包膜二十面体衣壳,通过特定种类的蚊子传播。它包含四种非结构蛋白,即nsP1、nsP2、nsP3和nsP4,由基因组5'端编码,以及五种结构蛋白,由基因组3'端编码,包括三种糖基化蛋白,即E1、E2、E3,一种64个氨基酸的小糖蛋白6K,和一种非糖基化核衣壳蛋白C。这种正链RNA甲病毒的表面覆盖着80个三聚体糖蛋白刺突,有助于病毒进入宿主细胞,每个刺突由三个E1-E2异二聚体拷贝组成。E2的前体p62的正确折叠以及E1-p62异二聚体的形成由E3控制,因此E3对于在甲病毒表面产生成熟刺突至关重要。最后,6K是一种64个氨基酸的小糖蛋白,有助于结构多蛋白转运至内质网,并将p62切割成成熟的结构蛋白E2。已证明CHIKV蛋白含有不同水平的内在无序性,通常包含内在无序蛋白区域(IDPRs)。IDPRs可与许多不相关的伙伴相互作用,且这些相互作用常伴随着从无序状态到有序状态的转变。IDPRs的相应子区域被认为是分子识别特征(MoRFs)。尽管已分析了CHIKV蛋白质组中IDPRs的存在情况,但截至目前尚未评估该病毒中基于无序的蛋白质-蛋白质相互作用(MoRF)的普遍性。为填补这一空白,在我们的研究中,我们利用了几种计算方法来识别CHIKV蛋白中的MoRFs区域。这些计算工具包括ANCHOR、DISOPRED3、MoRFpred和MoRFchibi_web服务器。这些分析揭示了所有CHIKV蛋白中都存在大量MoRF区域。未来,本研究结果可用于确定基孔肯雅病毒发病机制的本质,并可能有助于设计针对该病毒的药物。

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