Restored mutant receptor:Corticoid binding in chaperone complexes by trimethylamine N-oxideReportar como inadecuado




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Without a glucocorticoid GC ligand, the transcription factor glucocorticoid receptor GR is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide TMAO, on a conditions-dependent -activation-labile- mutant GR GRact-l, which under GR-activating conditions cannot bind GCs in cells or in cell cytosols. In both cells and cytosols, TMAO restores binding to GRact-l by stabilizing it in complex with chaperones. Cells bathed in much lower concentrations of TMAO than those required in vitro show restoration of GC binding, presumably due to intracellular molecular crowding effects.



Autor: Aaron L. Miller, W. Austin Elam, Betty H. Johnson, Shagufta H. Khan, Raj Kumar, E. Brad Thompson

Fuente: http://plos.srce.hr/



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