The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor

摘要: Abstract The human progesterone receptor form B (hPR-B) was expressed in Saccharomyces cerevisiae together with a specific reporter plasmid. To understand the mechanism underlying antagonist ligand activity, libraries of hormone binding domain (HBD)-mutated hPR-B molecules were prepared. A mutant identified that had lost ability to bind either or R5020; it could still RU486 and, surprisingly, fully activated transcription presence this "antagonist" and other antiprogestins. When assayed mammalian cells, again demonstrated agonistic activity. Sequence analysis indicated phenotype due truncation carboxy (C)-terminal 42 aa. We conclude amino acids extreme C-terminal region are required for progesterone, while antagonists site located more N-terminal HBD. Our results suggest contains an inhibitory function silences transactivation absence agonist antagonist.