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Type of Publication: | Journal article |
Publication status: | Published |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-2-1ua7g14yq6ibq5 |
Author: | Patel, Neha; Stengel, Florian; Aebersold, Ruedi; Gold, Matthew |
Year of publication: | 2017 |
Published in: | Nature communications ; 8 (2017), 1. - 1681. - eISSN 2041-1723 |
Pubmed ID: | 29162807 |
DOI (citable link): | https://dx.doi.org/10.1038/s41467-017-01715-w |
Summary: |
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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Subject (DDC): | 570 Biosciences, Biology |
Keywords: | Proteomics, X-ray crystallography |
Link to License: | Attribution 4.0 International |
Bibliography of Konstanz: | Yes |
PATEL, 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
@article{Patel2017-11-22Molec-40961, title={Molecular basis of AKAP79 regulation by calmodulin}, year={2017}, doi={10.1038/s41467-017-01715-w}, 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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