Molecular basis of AKAP79 regulation by calmodulin

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2017
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Patel, Neha
Aebersold, Ruedi
Gold, Matthew
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Nature communications ; 8 (2017), 1. - 1681. - eISSN 2041-1723
Abstract
AKAP79/150 is essential for coordinating second messenger-responsive enzymes in processes including synaptic long-term depression. Ca2+ 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 Ca2+-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 Ca2+-activated C-lobe and closed N-lobe cooperate to recognize a mixed α/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.
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570 Biosciences, Biology
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Proteomics, X-ray crystallography
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ISO 690PATEL, Neha, Florian STENGEL, Ruedi AEBERSOLD, Matthew GOLD, 2017. Molecular basis of AKAP79 regulation by calmodulin. In: Nature communications. 8(1), 1681. eISSN 2041-1723. Available under: doi: 10.1038/s41467-017-01715-w
BibTex
@article{Patel2017-11-22Molec-40961,
  year={2017},
  doi={10.1038/s41467-017-01715-w},
  title={Molecular basis of AKAP79 regulation by calmodulin},
  number={1},
  volume={8},
  journal={Nature communications},
  author={Patel, Neha and Stengel, Florian and Aebersold, Ruedi and Gold, Matthew},
  note={Article Number: 1681}
}
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