5NIN

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

5NIN の概要

• エントリーDOI: 10.2210/pdb5nin/pdb
• 分子名称: Calmodulin, A-kinase anchor protein 5, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: calmodulin, calcium, akap79, akap150, akap5, akap, ef hand, ca2+, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Membrane ; Lipid-anchor : P24588
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 38128.26

構造登録者

Gold, M.G.,Patel, N. (登録日: 2017-03-24, 公開日: 2017-12-06, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.7 Å)