3LL8
Crystal Structure of Calcineurin in Complex with AKAP79 Peptide
Summary for 3LL8
| Entry DOI | 10.2210/pdb3ll8/pdb |
| Descriptor | AKAP79 peptide, Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, Calcineurin subunit B type 1, ... (8 entities in total) |
| Functional Keywords | 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 |
| Biological source | Homo sapiens (human) More |
| Cellular location | Membrane ; Lipid-anchor : P24588 Cell membrane : Q08209 Cytoplasm, cytosol : P63098 |
| Total number of polymer chains | 5 |
| Total formula weight | 119733.84 |
| Authors | Li, H.,Hogan, P.G. (deposition date: 2010-01-28, release date: 2011-01-12, Last modification date: 2024-02-21) |
| Primary citation | 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 Cited by 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: 22343722DOI: 10.1038/nsmb.2238 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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