5NIN

Crystal Structure of AKAP79 calmodulin binding domain peptide in complex with Ca2+/Calmodulin

Summary for 5NIN

• Entry DOI: 10.2210/pdb5nin/pdb
• Descriptor: Calmodulin, A-kinase anchor protein 5, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: calmodulin, calcium, akap79, akap150, akap5, akap, ef hand, ca2+, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane ; Lipid-anchor : P24588
• Total number of polymer chains: 4
• Total formula weight: 38128.26

Authors

Gold, M.G.,Patel, N. (deposition date: 2017-03-24, release date: 2017-12-06, Last modification date: 2024-01-17)

Primary citation

Patel, N.,Stengel, F.,Aebersold, R.,Gold, M.G.
Molecular basis of AKAP79 regulation by calmodulin.
Nat Commun, 8:1681-1681, 2017

PubMed Abstract: AKAP79/150 is essential for coordinating second messenger-responsive enzymes in processes including synaptic long-term depression. Ca 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-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-activated C-lobe and closed N-lobe cooperate to recognize a mixed α/3 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.

PubMed: 29162807
DOI: 10.1038/s41467-017-01715-w

Experimental method

X-RAY DIFFRACTION (1.7 Å)