Predict Functionally Important Residues Responsible for Estrogen Receptor Subtype Divergence

摘要

The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the physiological effects of the female sex steroid hormone 17 beta estradiol (E2), and regulates the expression of genes involved in the growth, development and function of a diverge range of tissues. The ER is a member of nuclear receptor (NR) superfamily, which shares a common structural organization including six independent but interacting functional domains. Two ER subtypes, although related, are separate genesand code for proteins of differing lengths. We are interested in the selection constraint acting on the functional domains of ER subtypes after gene duplication. Because the sequence differences of ER subtype in ligand binding domain (LBD) provide the molecular basis for the subtype physiological function, it is necessary to identify those functional related sites in order to investigate the functional divergence between two subtypes. In this study, we utilize the evolutionary rate analysis approach, combined with structural mapping, to predict the functionally important residues responsible for ER subtype divergence.