A molecular dissection of the glycoprotein hormone receptors
In glycoprotein hormone receptors, a subfamily of rhodopsin-like G protein-coupled receptors, the recognition and activation steps are carried out by separate domains of the proteins. Specificity of recognition of the hormones [thyrotropin (TSH), lutropin (LH), human chorionic gonadotropin (hCG), follitropin (FSH)] involves leucine-rich repeats (LRR) present in an aminoterminal ectodomain and can be associated with a limited number of residues at key positions of the LRRs. The mechanism by which binding of the hormones results in activation is proposed to involve switching of the ectodomain from a tethered inverse agonist to a full agonist of the serpentine, rhodopsin-like portion of the receptor. Unexpectedly, the picture is complicated by the observation that promiscuous activation of one of the receptors (FSHr) by hCG or TSH can result from activating mutations affecting the serpentine portion of the receptors.
KeywordsMolecular Electrostatic Potential Luteinizing Hormone Receptor Thyrotropin Receptor Thyroid Adenoma Molecular Dissection
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