The molecular basis for protein kinase A anchoring revealed by solution NMR

Compartmentalization of signal transduction enzymes into signaling complexe s is an important mechanism to ensure the specificity of intracellular even ts, Formation of these complexes is mediated by specialized protein moths t hat participate in protein-protein interactions. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through i nteraction of the regulatory (R) subunit dimer with A-kinase-anchoring prot eins (AKAPs). We now report the solution structure of the type II PKA R-sub unit fragment RII alpha(1-44), which encompasses both the AKAP-binding and dimerization interfaces. This structure incorporates an X-type four-helix b undle dimerization motif with an extended hydrophobic face that is necessar y for high-affinity AKAP binding. NMR data on the complex between RII alpha (1-44) and an AKAP fragment reveals extensive contacts between the two prot eins. Interestingly, this same dimerization motif is present in other signa ling molecules, the S100 family. Therefore, the X-type four-helix bundle ma y represent a conserved fold for protein-protein interactions in signal tra nsduction.