The N-terminal region of the human progesterone A-receptor - Structural analysis and the influence of the DNA binding domain

The role of the N-terminal region in nuclear receptor function was addresse d by a biochemical and biophysical analysis of the progesterone receptor A- isoform lacking only the hormone binding domain (NT-A), Sedimentation studi es demonstrate that NT-A is quantitatively monomeric, with a highly asymmet ric shape. Contrary to dogma, the N-terminal region is structured as demons trated by limited proteolysis, However, N-terminal structure is strongly st abilized by the DNA binding domain, possibly explaining the lack, of struct ure seen in isolated activation domains, Upon DNA binding, NT-A undergoes N -terminal mediated assembly, suggestive of DNA-induced allostery, and consi stent with changes in protease accessibility of sites outside the DNA bindi ng domain. Microsequencing reveals that protease-accessible regions are lim ited to previously identified phosphorylation motifs and to functional doma in boundaries.