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Molecular Basis of D‐AKAP2 Binding to PKA Regulatory Subunits
Author(s) -
Sarma Ganapathy,
Kinderman Francis,
Kim Choel,
Daake Sventja,
Taylor Susan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.709.8
Subject(s) - gene isoform , protein subunit , protein kinase a , chemistry , c terminus , peptide , docking (animal) , binding site , computational biology , biochemistry , kinase , biology , amino acid , gene , medicine , nursing
cAMP‐dependent protein kinase (PKA) regulates a variety of biological activities by phosphorylating a broad range of target proteins. Spatial and temporal specificity of PKA activity is, in turn, achieved by a family of scaffolding proteins called as the A‐kinase anchoring proteins (AKAPs). One of these, dual‐specific AKAP 2 (D‐AKAP2) binds to both the Regulatory (R) isoforms (RI and RII) of PKA. Specifically, the dimerization and docking (D/D) domain at the N‐terminus of the R subunits forms a four‐helix bundle that provides an interface for AKAP binding. In order to understand the molecular basis of D‐AKAP2 binding to the RIα subunit and understand the molecular determinants that make D‐AKAP2 dual‐specific, we have solved the structures of the RIα D/D domain with and without the D‐AKAP2 peptide. The structure of the apo crystal form was solved using the anomalous signal from inherently present sulfur atoms. Together with the existing peptide array data and the RIIα D/D structure, the present structures reveal atomic‐level information on the dual‐specific nature of D‐AKAP2. The structures also provide insights into the role of a pair of highly conserved disulfides that might function as a redox sensor in cardiac myocytes. This work was supported by an American Heart Association Postdoctoral Fellowship to G.N.S, NIH grant to DK54441 to S.T and the Howard Hughes Medical Institute.