Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.
A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, MC 0654, La Jolla, CA 92093, USA.
Ganapathy N
GN
Sarma
Francis S
FS
Kinderman
Choel
C
Kim
Sventja
S
von Daake
Lirong
L
Chen
Bi-Cheng
BC
Wang
Susan S
SS
Taylor
D054758:A Kinase Anchor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D054743:Cyclic AMP-Dependent Protein Kinase Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity
D054758:A Kinase Anchor Proteins; C484639:AKAP10 protein, human; D004220:Disulfides; D054743:Cyclic AMP-Dependent Protein Kinase Type I