A canonical cation-π interaction stabilizes the agonist conformation of estrogen-like nuclear receptors

Representative crystal structures of the ligand-binding domain for the majority of nuclear receptors are currently available. A systematic comparative analysis of these structures identified an energetically favorable cation-π interaction that involves an amino acid located at the extreme C-terminal end and appears to form only in the agonist conformation of the estrogen receptor α, glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. It is postulated that this cation-π interaction is used by members of the estrogen-like subfamily to provide additional stabilization to the transcriptional active conformation upon ligand binding.