3LL8

Crystal Structure of Calcineurin in Complex with AKAP79 Peptide

3LL8 の概要

• エントリーDOI: 10.2210/pdb3ll8/pdb
• 分子名称: AKAP79 peptide, Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, Calcineurin subunit B type 1, ... (8 entities in total)
• 機能のキーワード: protein-peptide docking, protein targeting, calcineurin, akap79, beta-augmentation, calmodulin-binding, membrane, hydrolase, iron, metal-binding, nucleus, phosphoprotein, protein phosphatase, lipoprotein, myristate, hydrolase-calcium binding protein complex, hydrolase/calcium binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane ; Lipid-anchor : P24588; Cell membrane : Q08209; Cytoplasm, cytosol : P63098
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 119733.84

構造登録者

Li, H.,Hogan, P.G. (登録日: 2010-01-28, 公開日: 2011-01-12, 最終更新日: 2024-02-21)

主引用文献

Li, H.,Pink, M.D.,Murphy, J.G.,Stein, A.,Dell'acqua, M.L.,Hogan, P.G.
Balanced interactions of calcineurin with AKAP79 regulate Ca(2+)-calcineurin-NFAT signaling.
Nat.Struct.Mol.Biol., 19:337-345, 2012

PubMed Abstract: In hippocampal neurons, the scaffold protein AKAP79 recruits the phosphatase calcineurin to L-type Ca(2+) channels and couples Ca(2+) influx to activation of calcineurin and of its substrate, the transcription factor NFAT. Here we show that an IAIIIT anchoring site in human AKAP79 binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT, albeit more strongly. A modest decrease in calcineurin-AKAP affinity due to an altered anchoring sequence is compatible with NFAT activation, whereas a further decrease impairs activation. Counterintuitively, increasing calcineurin-AKAP affinity increases recruitment of calcineurin to the scaffold but impairs NFAT activation; this is probably due to both slower release of active calcineurin from the scaffold and sequestration of active calcineurin by 'decoy' AKAP sites. We propose that calcineurin-AKAP79 scaffolding promotes NFAT signaling by balancing strong recruitment of calcineurin with its efficient release to communicate with NFAT.

PubMed: 22343722
DOI: 10.1038/nsmb.2238

実験手法

X-RAY DIFFRACTION (2 Å)