Chen Yong-Xiang, Du Jin-Tang, Zhou Lian-Xiu, Liu Xiao-Hong, Zhao Yu-Fen, Nakanishi Hiroshi, Li Yan-Mei
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Chem Biol. 2006 Sep;13(9):937-44. doi: 10.1016/j.chembiol.2006.06.017.
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.
许多蛋白质中的丝氨酸和苏氨酸残基可通过磷酸化或N-乙酰葡糖胺化进行修饰。为了研究O-连接的N-乙酰葡糖胺（O-GlcNAc）和O-磷酸在调节小鼠雌激素受体β（mER-β）降解和活性中的相互作用机制，我们采用核磁共振技术、圆二色光谱（CD）和分子动力学模拟，研究了与mER-β N端内在无序（ID）区域对应的17肽模型中Ser(16)的O-GlcNAc化和O-磷酸化诱导的构象变化。我们的结果表明，O-磷酸化抑制了S(15)STG(18)片段中的转角形成。相反，O-GlcNAc化促进了该区域的转角形成。因此，我们推测，O-磷酸或O-GlcNAc修饰引起的mER-β N端S(15)STG(18)片段局部结构的不同变化可能会干扰mER-β ID区域的动态整体，这与其调节活性有关。
