Molecular mechanism by which palmitate inhibits PKR autophosphorylation.

ABSTRACT: PKR (double-stranded RNA-activated protein kinase) is an important component of the innate immunity, antiviral, and apoptotic pathways. Recently, our group found that palmitate, a saturated fatty acid, is involved in apoptosis by reducing the autophosphorylation of PKR at the Thr451 residue; however, the molecular mechanism by which palmitate reduces PKR autophosphorylation is not known. Thus, we investigated how palmitate affects the phosphorylation of the PKR protein at the molecular and biophysical levels. Biochemical and computational studies show that palmitate binds to PKR, near the ATP-binding site, thereby inhibiting its autophosphorylation at Thr451 and Thr446. Mutation studies suggest that Lys296 and Asp432 in the ATP-binding site on the PKR protein are important for palmitate bi

SUBMITTER: Cho H 

PROVIDER: S-EPMC3035770 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature