Fig. 5. Sequence alignments of the ligand-binding pockets of ancestral receptors compared to human ERα.

α-Helices that make up the LBD are boxed and numbered from 1 to 12 on the basis of the crystal structure from ERα (81). Amino acids from human ERα making direct hydrogen bonds with estradiol are highlighted in green. Amino acids making hydrophobic bonds with estradiol are highlighted in pink. Amino acids known to be involved in coactivator interaction are indicated with a star on top of each site. Differences with human ERα on ligand-binding or coactivator-binding sites are highlighted in yellow. Sequences of AncSR_AC and AncSR_D have been inferred in this study. The other ones come from previous analyses.