5hvz

Crystal structure of smAKAP AKB domain bound RIa dimerization/docking (D/D) complex at 2.0 A resolution

spinqualitylabelsall models 5hvz, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hvz is a 3 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAP0_BOVIN Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Publication Abstract from PubMed The A-kinase anchoring protein (AKAP) smAKAP has three extraordinary features; it is very small, it is anchored directly to membranes by acyl motifs, and it interacts almost exclusively with the type I regulatory subunits (RI) of cAMP-dependent kinase (PKA). Here, we determined the crystal structure of smAKAP's A-kinase binding domain (smAKAP-AKB) in complex with the dimerization/docking (D/D) domain of RIalpha which reveals an extended hydrophobic interface with unique interaction pockets that drive smAKAP's high specificity for RI-subunits. We also identify a conserved PKA phosphorylation site at Ser66 in the AKB domain which we predict would cause steric clashes and disrupt binding. This correlates with in vivo co-localization and fluorescence polarization studies where Ser66 AKB phosphorylation ablates RI-binding. Hydrogen/deuterium exchange studies confirm that the AKB helix is accessible and dynamic. Furthermore, full-length smAKAP as well as the unbound AKB is predicted to contain a break at the phosphorylation site, and circular dichroism measurements confirm that the AKB domain loses its helicity following phosphorylation. Since the active site of PKA's catalytic subunit does not accommodate alpha-helices, we predict that the inherent flexibility of the AKB domain enables its phosphorylation by PKA. This represents a novel mechanism, whereby activation of anchored PKA can terminate its binding to smAKAP affecting the regulation of localized cAMP-signaling events. This article is protected by copyright. All rights reserved. Structure of smAKAP and its regulation by PKA-mediated phosphorylation.,Burgers PP, Bruystens J, Burnley RJ, Nikolaev VO, Keshwani M, Wu J, Janssen BJ, Taylor SS, Heck AJ, Scholten A FEBS J. 2016 Mar 30. doi: 10.1111/febs.13726. PMID:27028580 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also A-kinase anchor protein 3D structures CAMP-dependent protein kinase 3D structures

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