title: A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes.
abstract: The specificity of intracellular signaling events is controlled, in part, by compartmentalization of protein kinases and phosphatases. The subcellular localization of these enzymes is often maintained by protein- protein interactions. A prototypic example is the compartmentalization of the cAMP-dependent protein kinase (PKA) through its association with A-kinase anchoring proteins (AKAPs). A docking and dimerization domain (D/D) located within the first 45 residues of each regulatory (R) subunit protomer forms a high affinity binding site for its anchoring partner. We now report the structures of two D/D-AKAP peptide complexes obtained by solution NMR methods, one with Ht31(493-515) and the other with AKAP79(392-413). We present the first direct structural data demonstrating the helical nature of the peptides. The structures reveal conserved hydrophobic interaction surfaces on the helical AKAP peptides and the PKA R subunit, which are responsible for mediating the high affinity association in the complexes. In a departure from the dimer-dimer interactions seen in other X-type four-helix bundle dimeric proteins, our structures reveal a novel hydrophobic groove that accommodates one AKAP per RIIalpha D/D.
authors: The Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0359, USA.
authors: M G
authors: MG
authors: Newlon
authors: M
authors: M
authors: Roy
authors: D
authors: D
authors: Morikis
authors: D W
authors: DW
authors: Carr
authors: R
authors: R
authors: Westphal
authors: J D
authors: JD
authors: Scott
authors: P A
authors: PA
authors: Jennings
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions
chemical_list: D002352:Carrier Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C400087:S Ht31; D012996:Solutions; D017868:Cyclic AMP-Dependent Protein Kinases