SOLUTION STRUCTURE OF A CYSTEINE-RICH DOMAIN OF RAT PROTEIN-KINASE-C

Intracellular protein phosphorylation by protein kinase C (PKC) plays a major role in the translation of extracellular signals into cellular events. Speculations on the structural basis for PKC activation are b ased on sequence homology between their cysteine-rich domains (CRD) an d the DNA-binding 'zinc-fingers'. We produced a fragment comprising th e second CRD (CRD2) of rat PKC-alpha and determined its three-dimensio nal structure in solution by NMR spectroscopy. This revealed that CRD2 adopts a globular fold allowing two non-consecutive sets of zinc-bind ing residues to form two separate metal-binding sites. The fold is dif ferent to those previously proposed and allows insight into the molecu lar topology of a family of homologous proteins.