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Structure. 2010 Feb 10;18(2):155-66. doi: 10.1016/j.str.2009.12.012.

Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.

Author information

1
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, MC 0654, La Jolla, CA 92093, USA.

Abstract

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.

PMID:
20159461
PMCID:
PMC3090270
DOI:
10.1016/j.str.2009.12.012
[Indexed for MEDLINE]
Free PMC Article

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