A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes

EMBO J. 2001 Apr 2;20(7):1651-62. doi: 10.1093/emboj/20.7.1651.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinases / chemistry*
  • Intercellular Signaling Peptides and Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Protein Structure, Secondary
  • Solutions


  • Carrier Proteins
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • S Ht31
  • Solutions
  • Cyclic AMP-Dependent Protein Kinases