Analysis of type 1 ryanodine receptor-12 kDa FK506-binding protein interaction.
Although dissociation of the 12 kDa FK506 binding protein (FKBP12)-type 1 ryanodine receptor (RyR1) complex by macrolide immunosuppressants is well documented, effects of many solutes and drugs have not been quantitated. In the current study, the influence of these on binding between solubilised RyR1 and an FKBP12-glutathione-S-transferase fusion protein was analysed using a novel assay. Association between these two proteins is stable, and is not greatly altered by changes in temperature, pH, cations, and endogenous solutes over physiological ranges. Ascomycin, an FK506 analogue, was identified for the first time as a drug which can disrupt the FKBP12-RyR1 complex.
Mackrill
J J
JJ
Department of Biochemistry, University College Cork, National University of Ireland, Cork, Ireland. stbi8042@ucc.ie
O'Driscoll
S
S
Lai
F A
FA
McCarthy
T V
TV
D000818:Animals; D005982:Glutathione Transferase / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D005982:Glutathione Transferase; D022021:Tacrolimus Binding Proteins