FIGURE 12.

Cartoon representations of the 3D crystal structure of ERα ligand-binding domain (LBD) homodimers (red-blue or blue-blue) in complex with estradiol (E2) (75) (A), 4-OH-tamoxifen (459) (B), raloxifene (75) (C), and lasofoxifene (509) (D). In A, occupancy of the ligand-binding pocket by E2 stabilizes helix 12 in a folded position (red arrow), revealing an interaction surface (AF-2) for coactivators (yellow star). In B–D, SERMs occupy the ligand-binding pocket but additionally contain a bulky side chain (underlined in red) which pushes helix 12 (light blue arrows) in front of AF-2, rendering it unavailable (red stars). Note that the crystal structure of ERα in complex with bazedoxifene is not yet available. Created using JSmol using structural data from the Protein Data Bank.