TY - JOUR
T1 - Analysis of type 1 ryanodine receptor-12 kDa FK506-binding protein interaction
AU - Mackrill, John J.
AU - O'Driscoll, Séan
AU - Lai, F. Anthony
AU - McCarthy, Tommie V.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - 12 kDa FK506-binding protein
KW - Macrolides
KW - Protein-protein interaction
KW - Ryanodine receptor
UR - https://www.scopus.com/pages/publications/0034800514
U2 - 10.1006/bbrc.2001.5125
DO - 10.1006/bbrc.2001.5125
M3 - Article
C2 - 11437371
AN - SCOPUS:0034800514
SN - 0006-291X
VL - 285
SP - 52
EP - 57
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -