title: The N-terminal region of the human progesterone A-receptor. Structural analysis and the influence of the DNA binding domain.
abstract: The role of the N-terminal region in nuclear receptor function was addressed by a biochemical and biophysical analysis of the progesterone receptor A-isoform lacking only the hormone binding domain (NT-A). Sedimentation studies demonstrate that NT-A is quantitatively monomeric, with a highly asymmetric shape. Contrary to dogma, the N-terminal region is structured as demonstrated by limited proteolysis. However, N-terminal structure is strongly stabilized by the DNA binding domain, possibly explaining the lack of structure seen in isolated activation domains. Upon DNA binding, NT-A undergoes N-terminal mediated assembly, suggestive of DNA-induced allostery, and consistent with changes in protease accessibility of sites outside the DNA binding domain. Microsequencing reveals that protease-accessible regions are limited to previously identified phosphorylation motifs and to functional domain boundaries.
authors.affiliation: Department of Medicine and Molecular Biology Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. david.bain@uchsc.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Bain
authors.forename: M A
authors.initials: MA
authors.lastname: Franden
authors.forename: J L
authors.initials: JL
authors.lastname: McManaman
authors.forename: G S
authors.initials: GS
authors.lastname: Takimoto
authors.forename: K B
authors.initials: KB
authors.lastname: Horwitz
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D010450:Endopeptidases / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D017510:Protein Folding; D011980:Receptors, Progesterone / Q000737:chemistry*; D020218:Response Elements; D014158:Transcription, Genetic
chemical_list: D011980:Receptors, Progesterone; C101118:progesterone receptor A; D004247:DNA; D010450:Endopeptidases