Kristalografska struktura kalcineurinskog heterodimera formirana od katalitičke (PPP3CA) i regulatorne (PPP3R1) podjedinice.[1]
Kalcineurin (CN) je proteinska fosfataza, takođe poznata kao proteinska fosfataza 3, i kalcijum-zavisna serin-treoninska fosfataza.[2]. On aktivira T ćelije imunskog sistema, i može se blokirati lekovima. Kalcineurin aktivira nuklearni faktor aktiviranih T ćelija, citoplazmni (NFATc) transkripcioni faktor, putem njegove defosforilacije. Aktivirani NFATc se zatim translocira u jedro, gde povećava izražavanje interleukina 2 (IL-2), koji zatim stimuliše rast i diferencijaciju T ćelijskog responsa. Kalcineurin je biološki cilj klase lekova pod nazivom kalcineurinski inhibitori, koja obuhvata ciklosporin, pimekrolimus i takrolimus.
Struktura
Kalcineurin je heterodimer od 61-kD kalmodulin-vezujuće katalitičke podjedinice, kalcineurina A i 19-kD Ca2+-vezujuće regulatorne podjedinice, kalcineurina B. Postoje tri izozima katalitčke podjedinice, svaka od kojih je kodirana zasebnim genom (PPP3CA, PPP3CB, i PPP3CC) i dve regulatorne izoforme, takođe kodirane zasebnim genima (PPP3R1, PPP3R2).
^PDB: 1AUI; Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW (1995). „Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex”. Nature. 378 (6557): 641—4. PMID 8524402. doi:10.1038/378641a0.
^Liu L, Zhang J, Yuan J, Dang Y, Yang C, Chen X, Xu J, Yu L (2005). „Crystal Characterization of a human regulatory subunit of protein phosphatase 3 gene (PPP3RL) expressed specifically in testis”. Mol Biol Rep. 32 (1): 41—45. PMID 15865209. doi:10.1007/s11033-004-4250-4.
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1aui: Ljudski kalcineurinski heterodimer
1m63: Kristalna struktura kalcineurin-ciklofilin-ciklosporina
1mf8: Kristalna struktura ljudskog kalcineurina u kompleksu sa ciklosporinom A i ljudskim ciklofilinom
1tco: Tercijarni kompleks fragmenta kalcineurina A, kalcineurina B, FKBP12 i imunosupresivnog leka FK506 (Takrolimus)
2jog: Struktura kalcineurin-NFAT kompleksa
2p6b: Kristalna struktura ljudskog kalcineurina u kompleksu sa PVIVIT peptidom
Molekularna i ćelijska biologija
Hemija
