Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan.
FEBS Lett. 2010 Mar 19;584(6):1119-25. doi: 10.1016/j.febslet.2010.02.055. Epub 2010 Feb 24.
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.
S100 蛋白是 EF 手型钙敏蛋白的一个亚家族，其确切的生物学功能尚未阐明。在这项工作中，我们已经确定亲环素 40（CyP40）和 FKBP52（称为免疫亲和素）是 S100 蛋白的新靶标。这些免疫亲和素有一个用于与 HSP90 结合的四肽重复（TPR）结构域。使用谷胱甘肽 S-转移酶下拉测定和免疫沉淀，我们已经证明 S100A1 和 S100A2 以 Ca2+依赖的方式特异性地与 FKBP52 和 CyP40 的 TPR 结构域相互作用，并导致 CyP40-Hsp90 和 FKBP52-Hsp90 相互作用的抑制。这些发现表明，Ca2+/S100 蛋白是免疫亲和素-Hsp90 复合物形成的 TPR 靶向调节剂。
