Desperately seeking...something

Published online this week in Structure, Wisely et al. present a high-resolution X-ray crystallographic structure of the ligand binding domain of human hepatocyte nuclear factor 4 gamma (HNF4gamma). They find fatty acids filling the ligand binding pocket of this receptor long considered an orphan, but these "ligands" appear to be locked into the protein and not readily amenable to exchange. Not only does this present a new paradigm for nuclear receptors but it also provides new insights into their evolutionary origins.