The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller
- 1 March 1998
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 392 (6671), 97-101
- https://doi.org/10.1038/32204
Abstract
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 temperatures1, 2. RCC1 homologues have been identified in many eukaryotes, including budding and fission yeast. Mutations in the gene affect pre-messenger RNA processing and transport3,4, mating5, initiation of mitosis6 and chromatin decondensation7, 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 Ran8; it increases the dissociation of Ran-bound GDP by 105-fold (ref. 9). It may also bind to DNA via a protein–protein complex2. Here we show that the structure of human RCC1, solved to 1.7-Å 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 -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.Keywords
This publication has 20 references indexed in Scilit:
- Crystal structure of the EF-Tu˙EF-Ts complex from Thermus thermophilusNature Structural & Molecular Biology, 1997
- A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X–linked retinitis pigmentosa (RP3)Nature Genetics, 1996
- The structure of the Escherichia coli EF-Tu· EF-Ts complex at 2.5 Å resolutionNature, 1996
- The Kinetic Mechanism of Ran-Nucleotide Exchange Catalyzed by RCC1Biochemistry, 1995
- DEMON/ANGEL: a suite of programs to carry out density modificationJournal of Applied Crystallography, 1995
- The ancient regulatory-protein family of WD-repeat proteinsNature, 1994
- Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constantsJournal of Applied Crystallography, 1993
- Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1Nature, 1991
- MOLSCRIPT: a program to produce both detailed and schematic plots of protein structuresJournal of Applied Crystallography, 1991
- Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation.Genes & Development, 1987