Activation of PKR: an open and shut case?
The double-stranded (ds) RNA-activated protein kinase, PKR, has a key role in the innate immunity response to viral infection in higher eukaryotes. PKR contains an N-terminal dsRNA-binding domain and a C-terminal kinase domain. In the prevalent autoinhibition model for PKR activation, dsRNA binding induces a conformational change that leads to the release of the dsRNA-binding domain from the kinase, thus relieving the inhibition of the latent enzyme. Structural and biophysical data now favor a model whereby dsRNA principally functions to induce dimerization of PKR via the kinase domain. This dimerization model has implications for other PKR regulatory mechanisms and represents a new structural paradigm for control of protein kinase activity.
Cole
James L
JL
Department of Molecular and Cell Biology, 91 N. Eagleville Road, U-3125 University of Connecticut, Storrs, CT 06269, USA. james.cole@uconn.edu
D000818:Animals; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D012330:RNA, Double-Stranded / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
D012330:RNA, Double-Stranded; D019892:eIF-2 Kinase