title: Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor beta.
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.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Du
authors.forename: Lian-Xiu
authors.initials: LX
authors.lastname: Zhou
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D000215:Acylation; D000818:Animals; D002942:Circular Dichroism; D003198:Computer Simulation; D047629:Estrogen Receptor beta / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D012694:Serine / Q000378:metabolism
chemical_list: D047629:Estrogen Receptor beta; D010455:Peptides; D012694:Serine; D000117:Acetylglucosamine