Chambraud B, Radanyi C, Camonis J H, Shazand K, Rajkowski K, Baulieu E E
INSERM (U33) and Collège de France, 80 rue du Général Leclerc, 94276 Bicêtre Cédex, France.
J Biol Chem. 1996 Dec 20;271(51):32923-9. doi: 10.1074/jbc.271.51.32923.
We have identified a human gene encoding a 48-kDa protein that specifically interacts with the peptidyl prolyl isomerase FK506-binding protein 59 (FKBP59) and also with the well known FKBP12. FKBP59 and FKBP12 belong to the large family of immunophilins that bind the macrolide immunosuppressant drugs FK506 and rapamycin. The yeast two-hybrid system was used to isolate target proteins that interact with the immunosuppressant drug binding domain of the rabbit FKBP59. The cDNA for an as yet unidentified protein was isolated and cloned from a Jurkat cell library. The cDNA sequence of 1804 base pairs reveals an open reading frame of 417 amino acids. In vitro experiments suggest a direct interaction between FKBP59 and this new target protein. This specific association seems to be restricted to the FKBP family, since it also occurs both in vivo and in vitro with FKBP12 but not with cyclophilin 40. This novel protein was named FKBP-associated protein (FAP48). The formation of the complexes between FKBP59 or FKBP12 and FAP48 is prevented by FK506 and rapamycin in a dose-dependent manner. These results suggest that FAP48 shares or overlaps the macrolide binding site on FKBP59 as well as on FKBP12 and therefore may represent a natural common ligand of these immunosuppressant drug receptors.
我们已经鉴定出一个编码48 kDa蛋白的人类基因，该蛋白能特异性地与肽基脯氨酰异构酶FK506结合蛋白59（FKBP59）相互作用，也能与著名的FKBP12相互作用。FKBP59和FKBP12属于亲免素大家族，该家族能结合大环内酯类免疫抑制药物FK506和雷帕霉素。利用酵母双杂交系统分离与兔FKBP59的免疫抑制药物结合结构域相互作用的靶蛋白。从Jurkat细胞文库中分离并克隆了一种尚未鉴定的蛋白的cDNA。1804个碱基对的cDNA序列揭示了一个417个氨基酸的开放阅读框。体外实验表明FKBP59与这种新的靶蛋白之间存在直接相互作用。这种特异性结合似乎仅限于FKBP家族，因为它在体内和体外也能与FKBP12发生结合，但不与亲环蛋白40结合。这种新蛋白被命名为FKBP相关蛋白（FAP48）。FK506和雷帕霉素以剂量依赖的方式阻止FKBP59或FKBP12与FAP48之间形成复合物。这些结果表明，FAP48在FKBP59以及FKBP12上共享或重叠大环内酯结合位点，因此可能代表这些免疫抑制药物受体的天然共同配体。
