Alternative O-GlcNAcylation/O-phosphorylation of ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor β

Summary 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 β (mER-β), 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-β 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-β caused by O-phosphate or O-GlcNAc modification might lead to the disturbances to the dynamic ensembles of the ID region of mER-β, which is related to its modulatory activity.