Structural highlights
Function
[AKAP5_HUMAN] May anchor the PKA protein to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with to the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade.
Publication Abstract from PubMed
AKAP79/150 is essential for coordinating second messenger-responsive enzymes in processes including synaptic long-term depression. Ca(2+) directly regulates AKAP79 through its effector calmodulin (CaM), but the molecular basis of this regulation was previously unknown. Here, we report that CaM recognizes a '1-4-7-8' pattern of hydrophobic amino acids starting at Trp79 in AKAP79. Cross-linking coupled to mass spectrometry assisted mapping of the interaction site. Removal of the CaM-binding sequence in AKAP79 prevents formation of a Ca(2+)-sensitive interface between AKAP79 and calcineurin, and increases resting cellular PKA phosphorylation. We determined a crystal structure of CaM bound to a peptide encompassing its binding site in AKAP79. CaM adopts a highly compact conformation in which its open Ca(2+)-activated C-lobe and closed N-lobe cooperate to recognize a mixed alpha/310 helix in AKAP79. The structure guided a bioinformatic screen to identify potential sites in other proteins that may employ similar motifs for interaction with CaM.
Molecular basis of AKAP79 regulation by calmodulin.,Patel N, Stengel F, Aebersold R, Gold MG Nat Commun. 2017 Nov 22;8(1):1681. doi: 10.1038/s41467-017-01715-w. PMID:29162807[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Patel N, Stengel F, Aebersold R, Gold MG. Molecular basis of AKAP79 regulation by calmodulin. Nat Commun. 2017 Nov 22;8(1):1681. doi: 10.1038/s41467-017-01715-w. PMID:29162807 doi:http://dx.doi.org/10.1038/s41467-017-01715-w
