Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor beta

Chem Biol. 2006 Sep;13(9):937-44. doi: 10.1016/j.chembiol.2006.06.017.

Abstract

Serine and threonine residues in many proteins can be modified by either phosphorylation or GlcNAcylation. To investigate the mechanism of O-GlcNAc and O-phosphate's reciprocal roles in modulating the degradation and activity of murine estrogen receptor beta (mER-beta), the conformational changes induced by O-GlcNAcylation and O-phosphorylation of Ser(16) in 17-mer model peptides corresponding to the N-terminal intrinsically disordered (ID) region of mER-beta were studied by NMR techniques, circular dichroism (CD), and molecular dynamics simulations. Our results suggest that O-phosphorylation discourages the turn formation in the S(15)STG(18) fragment. In contrast, O-GlcNAcylation promotes turn formation in this region. Thus, we postulate that the different changes of the local structure in the N-terminal S(15)STG(18) fragment of mER-beta caused by O-phosphate or O-GlcNAc modification might lead to the disturbances to the dynamic ensembles of the ID region of mER-beta, which is related to its modulatory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism
  • Acylation
  • Animals
  • Circular Dichroism
  • Computer Simulation
  • Estrogen Receptor beta / chemistry*
  • Estrogen Receptor beta / metabolism*
  • Mice
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry
  • Peptides / metabolism*
  • Phosphorylation
  • Protein Conformation
  • Protein Processing, Post-Translational*
  • Protein Structure, Secondary
  • Serine / metabolism

Substances

  • Estrogen Receptor beta
  • Peptides
  • Serine
  • Acetylglucosamine