Lamb J R, Michaud W A, Sikorski R S, Hieter P A
Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
EMBO J. 1994 Sep 15;13(18):4321-8. doi: 10.1002/j.1460-2075.1994.tb06752.x.
Cdc16p, Cdc23p and Cdc27p are all essential proteins required for cell cycle progression through mitosis in Saccharomyces cerevisiae. All three proteins contain multiple tandemly repeated 34 amino acid tetratricopeptide repeats (TPRs). Using two independent assays, two-hybrid analysis in vivo and co-immunoprecipitation in vitro, we demonstrate that Cdc16p, Cdc23p and Cdc27p self associate and interact with one another to form a macromolecular complex. A temperature sensitive mutation in the most highly conserved TPR domain of Cdc27p results in a greatly reduced ability to interact with Cdc23p, but has no effect on interactions with wild-type Cdc27p or Cdc16p. The specificity of this effect indicates that TPRs can mediate protein-protein interactions and that this mutation may define an essential interaction for cell cycle progression in yeast. The conservation of at least two of the three proteins from yeast to man suggests that this protein complex is essential for mitosis in a wide range of eukaryotes.
Cdc16p、Cdc23p和Cdc27p都是酿酒酵母有丝分裂过程中细胞周期进展所必需的蛋白质。这三种蛋白质都含有多个串联重复的34个氨基酸的四肽重复序列(TPR)。我们使用两种独立的检测方法,即体内双杂交分析和体外共免疫沉淀,证明Cdc16p、Cdc23p和Cdc27p能够自我结合并相互作用,形成一个大分子复合物。Cdc27p最高度保守的TPR结构域中的一个温度敏感突变导致其与Cdc23p相互作用的能力大大降低,但对与野生型Cdc27p或Cdc16p的相互作用没有影响。这种效应的特异性表明TPR可以介导蛋白质-蛋白质相互作用,并且这种突变可能定义了酵母细胞周期进展中的一种必需相互作用。从酵母到人类,这三种蛋白质中至少有两种具有保守性,这表明这种蛋白质复合物在广泛的真核生物中有丝分裂中是必需的。