Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1)

被引:195
作者
Renault, L [1 ]
Kuhlmann, J [1 ]
Henkel, A [1 ]
Wittinghofer, A [1 ]
机构
[1] Max Planck Inst Mol Physiol, D-44202 Dortmund, Germany
关键词
D O I
10.1016/S0092-8674(01)00315-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bound protein, is the guanine nucleotide exchange factor (GEF) for the nuclear GTP binding protein Ran. We report here the 1.8 Angstrom crystal structure of a Ran . RCC1 complex in the absence of nucleotide, an intermediate in the multistep GEF reaction. In contrast to previous structures, the phosphate binding region of the nucleotide binding site is perturbed only marginally, possibly due to the presence of a polyvalent anion in the P loop. Biochemical experiments show that a sulfate ion stabilizes the Ran . RCC1 complex and inhibits dissociation by guanine nucleotides. Based on the available structural and biochemical evidence, we present a unified scenario for the GEF mechanism where interaction of the P loop lysine with an acidic residue is a crucial element for the overall reaction.
引用
收藏
页码:245 / 255
页数:11
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