AKAP signaling islands constrain protein kinase A (PKA) and other effector proteins at specific regions of the cell. PKA anchoring is mediated by protein-protein interactions between the docking and dimerization domain of the regulatory subunits and an amphipathic helix of the AKAP. Preferential binding of the type I or the type II regulatory subunits to...
Hormones often transmit signals through adenosine 3’,5’-monophosphate (cAMP) cascades to promote protein phosphorylation at precise intracellular locations. The fidelity of these responses relies on the activation of anchored protein kinase A (PKA) holoenzymes. Using single-particle electron microscopy and other structural approaches we demonstrated that the anchoring protein AKAP79 constrains RII-C sub-assemblies within 150 to 250Å...
Beyond PKA: Scaffolding the subcellular architecture
Protein interaction domains create unique macromolecular complexes that drive evolution. By combining phylogenetic analyses with structural approaches, we have discovered that the docking and dimerization (D/D) domain of the protein kinase A regulatory (PKA-R) subunit is an ancient protein fold. Homology searching reveals a D/D domain superfamily with eighteen members that are conserved across most...
Intracellular diffusion of chemical signals is a molecular basis of cellular communication. This theory was originally predicated on the notion that all regulatory enzymes are soluble and move with a Brownian motion. Yet, these enzymes often have different roles in distinct subcellular compartments. Thus, compartmentalization of enzymes is now recognized as an important molecular mechanism...
