p53 is a negative regulator of cell growth. The majority of human tumors express mutant p53 proteins, which can be distinguished from wild-type by their immuno-reactivity to a panel of conformation-specific monoclonal antibodies, such as PAb421, PAb1620 and PAb246. Wild-type p53 has sequence-specific DNA binding activity. We demonstrate that upon binding DNA wild-type p53 changes conformation at both its N- and C-termini, such that it adopts a 'mutant'-like conformation. Very few of the known DNA binding proteins exhibit long-range conformational changes upon binding to DNA. Such proteins, like the Drosophila heat shock transcription factor, have DNA binding domains whose activity is regulated by conformation. The DNA binding activity, and therefore the function, of wild-type p53 may be regulated via its ability to adopt distinct conformations.