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

J Biol Chem. 2000 Mar 10;275(10):7313-20. doi: 10.1074/jbc.275.10.7313.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • DNA / metabolism*
  • Endopeptidases / pharmacology
  • Humans
  • Molecular Weight
  • Protein Folding
  • Receptors, Progesterone / chemistry*
  • Response Elements
  • Transcription, Genetic

Substances

  • Receptors, Progesterone
  • progesterone receptor A
  • DNA
  • Endopeptidases