The 1.7Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller
The 1.7Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller
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DOI：
10.1038/32204
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发表时间：
1998-03-05
期刊：
影响因子：
64.8
通讯作者：
Wittinghofer, A
中科院分区：
文献类型：
--
作者：
Renault, L;Nassar, N;Wittinghofer, A
编码染色体凝聚调节因子(RCC1)的基因被克隆，因为它能够补充仓鼠细胞系tsBN2的温度敏感表型，后者在不允许的温度(1-2)下，在细胞周期的G1期经历过早的染色体凝聚或停滞。RCC1同源物已经在许多真核生物中被鉴定出来，包括发芽酵母和分裂酵母。该基因的突变影响前信使RNA的加工和运输(3，4)、交配(5)、有丝分裂的启动(6)和染色质解缩(7)，这表明RCC1在控制核质运输和细胞周期中起着重要作用。在生物化学上，RCC1是核RAS同系物RAN(8)的鸟嘌呤核苷酸交换因子；它使RAN结合的GDP解离增加10(5)倍(参考文献)。9)。它也可能通过蛋白质-蛋白质复合体(2)与DNA结合。在这里，我们证明了人的RCC1的结构，用X射线结晶学解析到1.7埃的分辨率，由每个叶片51-68个残基的内部重复组成的七个叶片的螺旋桨组成。这些重复序列的序列和结构与WD40结构域蛋白不同，WD40结构域蛋白也形成七个叶片的螺旋桨，并包括G蛋白的β亚基。这种结构的性质解释了一系列已知突变的后果。参与鸟嘌呤核苷酸交换的蛋白质区域与被认为参与染色体结合的区域相对。
The gene encoding the regulator of chromosome condensation (RCC1) was cloned by virtue of its ability to complement the temperature-sensitive phenotype of the hamster cell line tsBN2, which undergoes premature chromosome condensation or arrest in the G1 phase of the cell cycle at non-permissive temperatures(1-2). RCC1 homologues have been identified in many eukaryotes, including budding and fission yeast. Mutations in the gene affect pre-messenger RNA processing and transport(3,4), mating(5), initiation of mitosis(6) and chromatin decondensation(7), suggesting that RCC1 is important in the control of nucleo-cytoplasmic transport and the cell cycle. Biochemically, RCC1 is a guanine-nucleotide-exchange factor for the nuclear Ras homologue Ran(8); it increases the dissociation of Ran-bound GDP by 10(5)-fold (ref. 9). It may also bind to DNA via a protein-protein complex(2). Here we show that the structure of human RCC1, solved to 1.7-Angstrom resolution by X-ray crystallography, consists of a seven-bladed propeller formed from internal repeats of 51-68 residues per blade. The sequence and structure of the repeats differ from those of WD40-domain proteins, which also form seven-bladed propellers and include the beta-subunits of G proteins. The nature of the structure explains the consequences of a wide range of known mutations. The region of the protein that is involved in guanine-nucleotide exchange is located opposite the region that is thought to be involved in chromosome binding.