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 RIα 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 RIIα:D-AKAP2 complex structure makes the mode of binding to RIα novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity. © 2010 Elsevier Ltd. All rights reserved.
Sarma, G. N., Kinderman, F. S., Kim, C., von Daake, S., Chen, L., Wang, B. C., & Taylor, S. S. (2010). Structure of D-AKAP2:PKA RI Complex: Insights into AKAP Specificity and Selectivity. Structure, 18(2), 155–166. https://doi.org/10.1016/j.str.2009.12.012