|2izx, resolution 1.30Å ()|
MOLECULAR BASIS OF AKAP SPECIFICITY FOR PKA REGULATORY SUBUNITS
Localization of cyclic AMP (cAMP)-dependent protein kinase (PKA) by A kinase-anchoring proteins (AKAPs) restricts the action of this broad specificity kinase. The high-resolution crystal structures of the docking and dimerization (D/D) domain of the RIIalpha regulatory subunit of PKA both in the apo state and in complex with the high-affinity anchoring peptide AKAP-IS explain the molecular basis for AKAP-regulatory subunit recognition. AKAP-IS folds into an amphipathic alpha helix that engages an essentially preformed shallow groove on the surface of the RII dimer D/D domains. Conserved AKAP aliphatic residues dominate interactions to RII at the predominantly hydrophobic interface, whereas polar residues are important in conferring R subunit isoform specificity. Using a peptide screening approach, we have developed SuperAKAP-IS, a peptide that is 10,000-fold more selective for the RII isoform relative to RI and can be used to assess the impact of PKA isoform-selective anchoring on cAMP-responsive events inside cells.
Molecular basis of AKAP specificity for PKA regulatory subunits., Gold MG, Lygren B, Dokurno P, Hoshi N, McConnachie G, Tasken K, Carlson CR, Scott JD, Barford D, Mol Cell. 2006 Nov 3;24(3):383-95. PMID:17081989
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.