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AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA

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Item Type:Article
Title:AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA
Creators Name:Götz, F. and Roske, Y. and Schulz, M.S. and Autenrieth, K. and Bertinetti, D. and Faelber, K. and Zühlke, K. and Kreuchwig, A. and Kennedy, E. and Krause, G. and Daumke, O. and Herberg, F.W. and Heinemann, U. and Klussmann, E.
Abstract:A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18{beta} bound to the D/D domain of the regulatory RII{alpha} subunits of PKA. We identified three hydrophilic anchor points in AKAP18{beta} outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. <em>In vitro</em> and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions.
Keywords:A-Kinase Anchoring Protein, Protein Kinase A, D/D Domain, PKA-Binding Domain, Protein-Protein Interaction, Compartmentalized cAMP Signalling
Source:Biochemical Journal
ISSN:0264-6021
Publisher:Portland Press (U.K.)
Volume:473
Number:13
Page Range:1881-1894
Date:28 June 2016
Official Publication:https://doi.org/10.1042/BCJ20160242
PubMed:View item in PubMed

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