Mechanisms of thyroid hormone action: insights from X-ray crystallographic and functional studies.

摘要: This review summarizes the studies conducted in our laboratory on mechanisms of thyroid hormone action over past two decades. We have attempted to place receptors (TRs) perspective with work by other investigators that established their nuclear localization, DNA-binding properties, DNA response elements, and role proteins involved TR-mediated regulation gene transcription. Recently, crystallographic TR ligand binding domain (LBD) revealed has a structural folding receptor's hydrophobic core. The analysis structure led biochemical genetic defined surfaces LBD required for dimerization coactivator proteins. Placement mutations found patients syndrome generalized resistance they were restricted amino acids vicinity pocket hormone. insights gained from elucidation will provide basis design compounds selective agonistic or antagonistic activities.