Structure of a p53 tetramer bound to the natural response element of the CDKN1A gene. The p53 tumor suppressor protein is inactivated in more than half of all human cancers. Although several p53-DNA structures have been determined, none of them includes a natural response element. The availability of a well-behaved p53 protein has allowed the determination of a structure containing four p53 subunits bound to the natural p53 response element of the CDKN1A gene. The structure reveals a marked conformational switch in loop L1 of the p53 DNA-binding domain that is even more extensive than the one previously observed in complexes of p53 with artificial consensus response elements. For further details, please see article by Emamzadah and coworkers on page 1493 in this issue.