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 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.
Bain
D L
DL
Department of Medicine and Molecular Biology Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. david.bain@uchsc.edu
Franden
M A
MA
McManaman
J L
JL
Takimoto
G S
GS
Horwitz
K B
KB
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
D011980:Receptors, Progesterone; C101118:progesterone receptor A; D004247:DNA; D010450:Endopeptidases