Peptides derived from the interferon-induced PKR prevent activation by HIV-1 TAR RNA

Abstract

The double-stranded RNA-dependent protein kinase (PKR) is believed to mediate cellular antiviral responses, function as a tumor suppressor, and regulate cell growth and differentiation. Its activation is dependent on double-stranded RNA (dsRNA) structures but these interactions are not fully understood. The possibility of direct interaction between dsRNA and the arginine and lysine-rich region of PKR (residues 54-74) was examined using synthetic peptides. We found that addition of a synthetic peptide corresponding to residues 54-74 of murine PKR or residues 60-80 of human PKR inhibited the autophosphorylation and activation of the kinase by either poly(I)-poly(C) or the 82-nucleotide-long TAR RNA. Gel-shift analysts indicated that the peptides disrupted the kinase-TAR complex by binding directly to TAR RNA. These findings delineate at least one dsRNA-binding domain in PKR which may be important for its cellular activation.