Activation of DAF-12 by mammalian bile acid(-like) metabolites.
A, 3-keto LCA (10 μm) activates the DAF-12s from S. stercoralis, A. caninum, and C. elegans in COS7 cells. B, (25S)-cholestenoic acid activates the DAF-12s from A. ceylanicum and C. elegans in a dose-dependent manner in HEK293 cells. RLU, relative light unit. C, comparison of the H-bonding network involved in ligand binding in the AceDAF-12 LBD-cholestenoic acid complex, DA complex a, and complex b. H-bonds are illustrated by white dashed lines with bond lengths noted in Å. The 1st number in parentheses indicates the bond length in the cholestenoic acid complex. The 2nd and 3rd number indicate the bond length in the (25S)-DA complex a and b, respectively. Rings of the steroid skeleton are labeled as A–D.