The atomic structure of nuclear receptor proteins reflects tinkering with an ancestral template. This cartoon rendering shows the superimposed atomic structures of five distantly related nuclear receptors that are activated by different chemical signals. The colored cylinders show the position of stable corkscrew-like helices in the receptor's atomic structure; the white strands show flexible loops. The chemical signals -- including hormones, fatty acids, retinoids and other molecules -- are shown as gray spheres. The ability of the proteins to be activated by different signals is due to subtle changes in the size and surface properties of the "pocket" where the signal binds, not a fundamental redesign of the receptor structure.