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The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller

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 β-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.

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Figure 1: Overall three-dimensional structure of RCC1.
Figure 2: Primary- and secondary-structure alignment.
Figure 3: The structure of the RCC1 repeat.

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Acknowledgements

L.R. thanks the IBS/LCCP and the French Ministère de la Recherche et de l'Education for support and the staff at the European synchotron radiation facility (ESRF) on the beam-line CRG D2AM for help. We thank the HFSP (A.W.); R. Schebaum for secretarial assistance; C.Nowak, N. Gülüm and M. Schulte-Spechtel for technical assistance; W. Kabsch and F. Vellieux for advice; the staff at the synchrotron facilities EMBL c/o DESY for support; B. Prakash for reading the manuscript and for discussions; and M. Hess for help with figures.

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Correspondence to Alfred Wittinghofer.

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Renault, L., Nassar, N., Vetter, I. et al. The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller. Nature 392, 97–101 (1998). https://doi.org/10.1038/32204

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