CRYSTAL-STRUCTURE OF THE NUCLEAR RAS-RELATED PROTEIN RAN IN ITS GDP-BOUND FORM

THE Ran proteins constitute a distinct branch of the superfamily of Ra s-related GTP-binding proteins(1) which function as molecular switches cycling between GTP-bound 'on' and GDP-bound 'off' states(2). Ran is located predominantly in the nucleus of eukaryotic cells(3) and is inv olved in the nuclear import of proteins(4,5) as well as in control of DNA synthesis and of cell-cycle progression(6-8). We report here the c rystal structure at 2.3 Angstrom resolution of human Ran (M(r) 24K) co mplexed with GDP and Mg2+. This structure reveals a similarity with th e Ras core (G-domain) but with significant variations in regions invol ved in GDP and Mg2+ coordination (switch I and switch II regions in Ra s)(9,10), suggesting that there could be major conformational changes upon GTP binding. In addition to the G-domain, an extended chain and a n alpha-helix were identified at the carboxy terminus. The amino-termi nal (amino-acid residues (1)MAAQGEP(7)) stretch and the acidic tail (( 211)DEDDDL(216)) appear to be flexible in the crystal structure.