Commentary Cell Science Reviews Vol 5 No 4 ISSN 1742-8130

Evolution of PKR combats viral mimicry

The innate immune system provides the first line of host defense to pathogens. Part of this response is mediated by the cellular RNA-activated protein kinase, PKR. In a recent article published in the journal Nature [1], findings on the rate of evolution of PKR and how it relates to K3L, a pseudosubstrate viral mimic from poxviruses, are presented. The authors employ an impressive diversity of approaches, including phylogenetic analyses of PKR from 21 primates as well as functional yeast growth assays, both of which are interpreted at the molecular level using crystal structures. Phylogenetic analyses reveal positive selection throughout PKR and K3L, but little or no change in the sequence of PKR’s true cellular substrate eIF2α or the three other cellular kinases that phosphorylate it. Thus, certain genes in the primate genome are capable of evolving rapidly. Functional assays conducted on mutant PKRs in which a subset of the positively selected residues was changed confirm that certain amino acids confer species-specific resistance to K3L. Rapid evolution of genes involved in innate immunity may be a mechanism for keeping pace with viral challenges.

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