A model is presented for the regulation of the double-stranded RNA (ds
RNA)-activated mammalian protein kinase PKR, which is involved in prot
ein synthesis inhibition and the antiviral response in cells. A series
of previous findings abut PKR (O) over tilde s behavior are reviewed,
including its effects on translation; the activation of its protein k
inase activity; binding sites for PKR on RNA; PKR (O) over tilde s pro
tein domains, which include two double-stranded RNA binding motifs (ds
RBMs); and the likelihood of PKR dimer formation. The model which emer
ges to account for many of these observations includes the suggestion
that PKR dimers form which are stabilized and rearranged upon binding
to dsRNA regions 60 bp or longer. The hypothesis includes protein conf
ormational changes within each member of a PKR dimer bound to dsRNA wh
ich re-position an inhibitory polypeptide domain and thus allow kinase
activation. Also considered are ways in which PKR interacts with impe
rfectly duplexed, highly structured RNA molecules.