4ZP3

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

Summary for 4ZP3

• Entry DOI: 10.2210/pdb4zp3/pdb
• Descriptor: cAMP-dependent protein kinase type II-alpha regulatory subunit, A-kinase anchor protein 7 isoforms alpha and beta, CADMIUM ION, ... (4 entities in total)
• Functional Keywords: anchor points, amphiphathic helix, akap, dd-domain, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P13861; Isoform Alpha: Lateral cell membrane; Lipid- anchor. Isoform Beta: Apical cell membrane; Lipid- anchor: O43687
• Total number of polymer chains: 18
• Total formula weight: 87385.71

Authors

Goetz, F.,Roske, Y.,Faelber, K.,Zuehlke, K.,Autenrieth, K.,Kreuchwig, A.,Krause, G.,Herberg, F.W.,Daumke, O.,Heinemann, U.,Klussmann, E. (deposition date: 2015-05-07, release date: 2016-05-04, Last modification date: 2024-05-08)

Primary citation

Gotz, F.,Roske, Y.,Schulz, M.S.,Autenrieth, K.,Bertinetti, D.,Faelber, K.,Zuhlke, K.,Kreuchwig, A.,Kennedy, E.J.,Krause, G.,Daumke, O.,Herberg, F.W.,Heinemann, U.,Klussmann, E.
AKAP18:PKA-RII alpha structure reveals crucial anchor points for recognition of regulatory subunits of PKA.
Biochem.J., 473:1881-1894, 2016

PubMed 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 AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β 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. In vitro 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.

PubMed: 27102985
DOI: 10.1042/BCJ20160242

Experimental method

X-RAY DIFFRACTION (2.63 Å)