X-Ray Crystal Structure of the Ancestral 3-Ketosteroid Receptor–Progesterone–Mifepristone Complex Shows Mifepristone Bound at the Coactivator Binding Interface
Figure 5
Mifepristone occupies the coactivator protein space.
A. ancSR2–progesterone–mifepristone (protein, slate blue; mifepristone, magenta) was overlaid with ancestral corticoid receptor–deoxycorticosterone–hSHP NRBox1 (PDB accession code: 2Q3Y) complex. Mifepristone occupies the same space as the hSHP NRBox1 peptide (green, leucine side chains shown as sticks). B. Sequence alignment of ancestral and extant 3-ketosteroid receptor coactivator binding clefts. Sequence alignments of the AncSR2, AncCR, Progesterone Receptor (PR), Androgen Receptor (AR), Glucocorticoid Receptor (GR), and Mineralocorticoid Receptor (MR) coactivator binding clefts. Hydrophobic interactions (green) and hydrogen bonds (red) are shown for the interaction between AncSR2–mifepristone site-two and AncCR–SHP. Conserved residues across the SR lineage are indicated by a black box.