Systematic characterization of the local evolutionary space available to human PKR and vaccinia virus K3.

ABSTRACT: The interfaces between host and viral proteins can be dynamic spaces in which genetic variants are continually pursued, giving rise to evolutionary arms races.  One such scenario is found between the mammalian innate immunity protein PKR (protein kinase R) and the poxvirus antagonist K3.  Once activated, PKR phosphorylates the natural substrate eIF2α, which halts protein synthesis within the cell and prevents viral replication. K3 acts as a pseudosubstrate antagonist against PKR by directly antagonizing this halt in protein synthesis, enabling poxviruses to replicate in the cell. Exploring the impact of genetic variants in both PKR and K3 is necessary not only to highlight residues of evolutionary constraint and opportunity but also to elucidate the mechanism by which human PKR is able to

SUBMITTER: Chambers MJ 

PROVIDER: S-EPMC10705557 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature