Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor beta.
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.
Chen
Yong-Xiang
YX
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Du
Jin-Tang
JT
Zhou
Lian-Xiu
LX
Liu
Xiao-Hong
XH
Zhao
Yu-Fen
YF
Nakanishi
Hiroshi
H
Li
Yan-Mei
YM
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
D047629:Estrogen Receptor beta; D010455:Peptides; D012694:Serine; D000117:Acetylglucosamine