A STRUCTURAL ROLE FOR METAL-IONS IN THE WILD-TYPE CONFORMATION OF THETUMOR SUPPRESSOR PROTEIN-P53

In human tumors, many different point mutations of the p53 gene knock out suppressor function and induce the p53 polypeptide to adopt an imm unologically distinct, ''mutant'' conformation. Here we show that expo sure to the metal chelator 1,10-phenanthroline induces wild-type p53 t o adopt the mutant conformation and that this process is reversible. C onversion to mutant phenotype also occurs after exposure to (a) an org anic mercurial reagent targeting cysteinyl residues and (b) low concen trations of mercury or cadmium. We propose that binding of metal ions, most probably zinc, to conserved cysteinyl residues stabilizes the te rtiary structure of wild-type p53.