Activation of the estrogen receptor-a (ER-α). Ribbon diagram shows ER-α (yellow) bound to a peptide of the Grip1 coactivator (red) and to the ER-α agonist tetrahydrocrysene (blue). ER-α has well-known roles in the progression and treatment of breast and uterine cancer, whereas ER-β contributes to resistance to prostate and colon cancer. This structure defines features that are required for tetrahydrocrysene to act as an ER-α agonist, but as an antagonist of ER-β, and it reveals the mechanism of ligand-selective signaling. Work and image done in the laboratory of Assistant Professor Kendall W. Nettles.