Статья

Comprehensive Intrinsic Disorder Analysis of 6108 Viral Proteomes: From the Extent of Intrinsic Disorder Penetrance to Functional Annotation of Disordered Viral Proteins

N. Kumar, R. Kaushik, C. Tennakoon, V. Uversky, S. Longhi, K. Zhang, S. Bhatia,
2021

Much of our understanding of proteins and proteomes comes from the traditional protein structure-function paradigm. However, in the last 2 decades, both computational and experimental studies have provided evidence that a large fraction of functional proteomes across different domains of life consists of intrinsically disordered proteins, thus triggering a quest to unravel and decipher protein intrinsic disorder. Unlike structured/ordered proteins, intrinsically disordered proteins/regions (IDPs/IDRs) do not possess a well-defined structure under physiological conditions and exist as highly dynamic conformational ensembles. In spite of this peculiarity, these proteins have crucial roles in cell signaling and regulation. To date, studies on the abundance and function of IDPs/IDRs in viruses are rather limited. To fill this gap, we carried out an extensive and thorough bioinformatics analysis of 283â »000 proteins from 6108 reference viral proteomes. We analyzed protein intrinsic disorder from multiple perspectives, such as abundance of IDPs/IDRs across diverse virus types, their functional annotations, and subcellular localization in taxonomically divergent hosts. We show that the content of IDPs/IDRs in viral proteomes varies broadly as a function of virus genome types and taxonomically divergent hosts. We have combined the two most commonly used and accurate IDP predictors' results with charge-hydropathy (CH) versus cumulative distribution function (CDF) plots to categorize the viral proteins according to their IDR content and physicochemical properties. Mapping of gene ontology on the disorder content of viral proteins reveals that IDPs are primarily involved in key virus-host interactions and host antiviral immune response downregulation, which are reinforced by the post-Translational modifications tied to disorder-enriched viral proteins. The present study offers detailed insights into the prevalence of the intrinsic disorder in viral proteomes and provides appealing targets for the design of novel therapeutics.

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  • 1. Version of Record от 2021-01-01

Метаданные

Об авторах
  • N. Kumar
    ICAR - National Institute of High Security Animal Diseases, Bhopal
  • R. Kaushik
    Riken
  • C. Tennakoon
    The Pirbright Institute
  • V. Uversky
    Morsani College of Medicine, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences
  • S. Longhi
    Aix Marseille Université
  • K. Zhang
    Riken
  • S. Bhatia
    ICAR - National Institute of High Security Animal Diseases, Bhopal
Название журнала
  • Journal of Proteome Research
Финансирующая организация
  • Centre National de la Recherche Scientifique
Номер гранта
  • CRG/2020/001274
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC BY
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus