THE 1.7-ANGSTROM CRYSTAL-STRUCTURE OF THE REGULATOR OF CHROMOSOME CONDENSATION (RCC1) REVEALS A 7-BLADED PROPELLER

The gene encoding the regulator of chromosome condensation (RCC1) was cloned by virtue of its ability to complement the temperature-sensitiv e 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 identifie d in many eukaryotes, including budding and fission yeast. Mutations i n the gene affect pre-messenger RNA processing and transport(3,4), mat ing(5), initiation of mitosis(6) and chromatin decondensation(7), sugg esting that RCC1 is important in the control of nucleo-cytoplasmic tra nsport and the cell cycle. Biochemically, RCC1 is a guanine-nucleotide -exchange factor for the nuclear Ras homologue Ran(8); it increases th e dissociation of Ran-bound GDP by 10(5)-fold (ref. 9). It may also bi nd to DNA via a protein-protein complex(2). Here we show that the stru cture of human RCC1, solved to 1.7-Angstrom resolution by X-ray crysta llography, consists of a seven-bladed propeller formed from internal r epeats of 51-68 residues per blade. The sequence and structure of the repeats differ from those of WD40-domain proteins, which also form sev en-bladed propellers and include the beta-subunits of G proteins. The nature of the structure explains the consequences of a wide range of k nown 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.