Androgen receptor (ligand binding domain) (AR (LBD))

The **androgen receptor ligand binding domain** is the C-terminal region of the androgen receptor that binds steroid hormones such as testosterone and dihydrotestosterone[3][4]. This binding induces conformational changes essential for receptor activation, dimerization, and interaction with coactivator proteins, ultimately triggering the transcription of target genes involved in male sexual development, tissue growth, and metabolism[1][8]. The AR LBD's structure has been resolved by X-ray crystallography and is characterized by a typical nuclear receptor fold composed of multiple alpha-helices forming a ligand binding pocket[3][4][8]. The domain contains an activation function (AF-2) surface for coregulator interaction, and is the site of numerous disease-associated mutations that alter response to therapy, especially in prostate cancer[5][7]. Drugs targeting the AR LBD include agonists, antagonists, and SARMs, with antagonists being a mainstay of prostate cancer therapy. Mutational changes in the domain contribute to therapy resistance and present clinical challenges[5][7].

Other names

AR ligand binding domainAR LBDAndrogen receptor C-terminal domainSteroid hormone receptor ligand binding domain (less specific)

Agonists (e.g., androgens) bind the LBD, induce conformational change, and activate transcriptional regulation of androgen-responsive genes. Antagonists bind the LBD, prevent androgens from binding, and block receptor activation and transcriptional effects. SARMs (selective androgen receptor modulators) induce tissue-selective effects by modulating the receptor's conformation and downstream gene expression.