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A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes
Author(s) -
Newlon Marceen G.,
Roy Melinda,
Morikis Dimitrios,
Carr Daniel W.,
Westphal Ryan,
Scott John D.,
Jennings Patricia A.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.7.1651
Subject(s) - protein subunit , biology , compartmentalization (fire protection) , protein kinase a , dimer , anchoring , biochemistry , protein structure , biophysics , peptide , microbiology and biotechnology , kinase , enzyme , chemistry , organic chemistry , structural engineering , gene , engineering
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 RIIα D/D.