Evolutionary conservation of Ebola virus proteins predicts important functions at residue level

Bioinformatics. 2017 Jan 15;33(2):151-154. doi: 10.1093/bioinformatics/btw610. Epub 2016 Sep 21.

Abstract

Motivation: The recent outbreak of Ebola virus disease (EVD) resulted in a large number of human deaths. Due to this devastation, the Ebola virus has attracted renewed interest as model for virus evolution. Recent literature on Ebola virus (EBOV) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. But no study yet, has focused on the conservation patterns of EBOV proteins.

Results: We analyzed the evolution of functional regions of EBOV and highlight the function of conserved residues in protein activities. We apply an array of computational tools to dissect the functions of EBOV proteins in detail: (i) protein sequence conservation, (ii) protein-protein interactome analysis, (iii) structural modeling and (iv) kinase prediction. Our results suggest the presence of novel post-translational modifications in EBOV proteins and their role in the modulation of protein functions and protein interactions. Moreover, on the basis of the presence of ATM recognition motifs in all EBOV proteins we postulate a role of DNA damage response pathways and ATM kinase in EVD. The ATM kinase is put forward, for further evaluation, as novel potential therapeutic target.

Availability and implementation: http://www.biw.kuleuven.be/CSB/EBOV-PTMs CONTACT: vera.vannoort@biw.kuleuven.beSupplementary information: Supplementary data are available at Bioinformatics online.

MeSH terms

  • Amino Acid Sequence
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Conserved Sequence*
  • DNA Damage
  • DNA Repair
  • Ebolavirus / genetics
  • Ebolavirus / metabolism*
  • Evolution, Molecular*
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Models, Molecular
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Proteomics
  • Viral Proteins / metabolism*

Substances

  • Viral Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins