S100 proteins regulate the interaction of Hsp90 with Cyclophilin 40 and FKBP52 through their tetratricopeptide repeats.
S100 proteins are a subfamily of the EF-hand type calcium sensing proteins, the exact biological functions of which have not been clarified yet. In this work, we have identified Cyclophilin 40 (CyP40) and FKBP52 (called immunophilins) as novel targets of S100 proteins. These immunophilins contain a tetratricopeptide repeat (TPR) domain for Hsp90 binding. Using glutathione-S transferase pull-down assays and immunoprecipitation, we have demonstrated that S100A1 and S100A2 specifically interact with the TPR domains of FKBP52 and CyP40 in a Ca(2+)-dependent manner, and lead to inhibition of the CyP40-Hsp90 and FKBP52-Hsp90 interactions. These findings have suggested that the Ca(2+)/S100 proteins are TPR-targeting regulators of the immunophilins-Hsp90 complex formations.
Shimamoto
Seiko
S
Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan.
Kubota
Yasuo
Y
Tokumitsu
Hiroshi
H
Kobayashi
Ryoji
R
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000494:pharmacology; D002522:Chlorocebus aethiops; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000737:chemistry / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020104:Immunophilins / Q000737:chemistry / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D009418:S100 Proteins / Q000378:metabolism / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism*
D000081406:Peptidyl-Prolyl Isomerase F; D018841:HSP90 Heat-Shock Proteins; D046912:Multiprotein Complexes; D009418:S100 Proteins; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4; D020104:Immunophilins; D002118:Calcium