Yoo, J., Ko, S., Kim, H., Sampson, H., Yun, J.H., Choe, K.M., Chang, I., Arrowsmith, C.H., Krause, H.M., Cho, H.S., Lee, W. (2011). Crystal structure of fushi tarazu factor 1 ligand binding domain/fushi tarazu Peptide complex identifies new class of nuclear receptors.  J. Biol. Chem. 286(36): 31225--31231.

FBrf0215056

Research paper

The interaction between the orphan nuclear receptor FTZ-F1 (Fushi tarazu factor 1) and the segmentation gene protein FTZ is critical for specifying alternate parasegments in the Drosophila embryo. Here, we have determined the structure of the FTZ-F1 ligand-binding domain (LBD)·FTZ peptide complex using x-ray crystallography. Strikingly, the ligand-binding pocket of the FTZ-F1 LBD is completely occupied by helix 6 (H6) of the receptor, whereas the cofactor FTZ binds the co-activator cleft site of the FTZ-F1 LBD. Our findings suggest that H6 is essential for transcriptional activity of FTZ-F1; this is further supported by data from mutagenesis and activity assays. These data suggest that FTZ-F1 might belong to a novel class of ligand-independent nuclear receptors. Our findings are intriguing given that the highly homologous human steroidogenic factor-1 and liver receptor homolog-1 LBDs exhibit sizable ligand-binding pockets occupied by putative ligand molecules.

PMC3173125 (PMC) (EuropePMC)