Analysis of type 1 ryanodine receptor-12 kDa FK506-binding protein interaction

Although dissociation of the 12 kDa FK506 binding protein (FKBP12)-type 1 r yanodine receptor (RyR1) complex by macrolide immunosuppressants is well do cumented, effects of many solutes and drugs have not been quantitated, In t he current study, the influence of these on binding between solubilised RyR 1 and an FKBP12-glutathione-S-transferase fusion protein was analysed using a novel assay. Association between these two proteins is stable, and is no t greatly altered by changes in temperature, pH, cations, and endogenous so lutes over physiological ranges. Ascomycin, an FK506 analogue, was identifi ed for the first time as a drug which can disrupt the FKBP12-RyR1 complex. (C) 2001 Academic Press.