Structure of D-AKAP2:PKA RI Complex: Insights into AKAP Specificity and Selectivity

Journal Article · Mon Nov 22 04:00:00 EST 2010 · Structure

DOI:https://doi.org/10.1016/j.str.2009.12.012· OSTI ID:1002764

Sarma, Ganapathy N; Kinderman, Francis S; Kim, Choel; von Daake, Sventja; Chen, Lirong; Wang, Bi-Cheng; Taylor, Susan S ^[1]

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1. UCSD

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 RI{alpha} 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 RII{alpha}:D-AKAP2 complex structure makes the mode of binding to RI{alpha} novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002764
• Journal Information: Structure, Journal Name: Structure Journal Issue: (2) ; 02, 2010 Vol. 18
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AFFINITY
DISULFIDES
FASTENING
PHOSPHOTRANSFERASES
PROTEINS
SPECIFICITY