Galat A, Lane W S, Standaert R F, Schreiber S L
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
Biochemistry. 1992 Mar 3;31(8):2427-34. doi: 10.1021/bi00123a031.
FKBP25, a previously uncharacterized 25-kDa FK506- and rapamycin-binding protein, was purified to homogeneity from calf thymus, brain, and spleen, and the sequence of a 215 amino acid (aa) 24-kDa C-terminal peptide was established. The N-terminal domain (101 aa) is unrelated to any known protein, is hydrophilic, and is predicted by circular dichroism spectroscopy to be largely alpha-helix. The C-terminal domain (114 aa) is homologous to FKBP12 and other FKBPs but has a potential nuclear targeting sequence and a unique insertion of seven amino acids in one of its loops. FKBP25 displays the rotamase activity characteristic of FKBPs; the activity is inhibited by the immunosuppressants rapamycin (Ki = 0.9 nM) and FK506 (Ki = 160 nM), but not cyclosporin A. The protein, its rapamycin selectivity, and the potential nuclear targeting sequence are discussed in terms of the structure of hFKBP12.
FKBP25是一种以前未被鉴定的25 kDa的FK506和雷帕霉素结合蛋白，从小牛胸腺、大脑和脾脏中纯化至同质，并确定了一个215个氨基酸（aa）的24 kDa C末端肽的序列。N末端结构域（101个氨基酸）与任何已知蛋白质无关，具有亲水性，通过圆二色光谱预测其主要为α螺旋结构。C末端结构域（114个氨基酸）与FKBP12和其他FKBP同源，但具有潜在的核靶向序列，并且在其一个环中有一个独特的七个氨基酸插入。FKBP25表现出FKBP特有的肽基脯氨酰顺反异构酶活性；该活性受到免疫抑制剂雷帕霉素（Ki = 0.9 nM）和FK506（Ki = 160 nM）的抑制，但不受环孢素A的抑制。本文根据hFKBP12的结构对该蛋白、其对雷帕霉素的选择性以及潜在的核靶向序列进行了讨论。
