FIG. 13.

A model for PKR activation. The dimerization and dsRNA-binding domain of the protein is shown as a circle. The hydrophobic side of the α helix within this domain is shaded black, and the charged side is shaded gray. The catalytic domain of the protein is shown as a filled square in the inactive state and as an open oval in the active state. Dots on the stems denote ATP-binding sites, either accessible (open dots) or not accessible (solid dots) to ATP. “P” denotes phosphorylation of the protein, and squiggly lines denote dsRNA. Inactive PKR monomers and dimers exist in equilibrium. The dimerization is mediated by interactions between the hydrophobic sides of the α helix. dsRNA can bind to the charged side of either monomers or dimers, but only the latter leads to a conformational change, ATP binding, intermolecular autophosphorylation, and acquisition of enzyme activity. Heparin, on the other hand, binds to monomers and causes a different conformational change leading to ATP binding, intramolecular autophosphorylation, and enzyme activation.