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

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.

SUBMITTER: Sarma GN

PROVIDER: S-EPMC3090270 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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

Sarma Ganapathy N GN Kinderman Francis S FS Kim Choel C von Daake Sventja S Chen Lirong L Wang Bi-Cheng BC Taylor Susan S SS

Structure (London, England : 1993) 20100201 2

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 ...[more]

PMID: 20159461

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