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

RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bou nd 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 t he multistep GEF reaction. In contrast to previous structures, the phosphat e binding region of the nucleotide binding site is perturbed only marginall y, possibly due to the presence of a polyvalent anion in the P loop. Bioche mical experiments show that a sulfate ion stabilizes the Ran . RCC1 complex and inhibits dissociation by guanine nucleotides. Based on the available s tructural and biochemical evidence, we present a unified scenario for the G EF mechanism where interaction of the P loop lysine with an acidic residue is a crucial element for the overall reaction.