在O-GlcNAc转移酶的活性部位中,HCF-1被切割
Michael B Lazarus1, Jiaoyang Jiang, Vaibhav Kapuria
1Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
概括
与O结合的N-乙糖胺 (O-GlcNAc) 转移酶 (OGT) 在其活性部位内切割宿主细胞因子-1 (HCF-1). 这表明O-GlcNAc蛋白质糖化和HCF-1裂变共享相同的酶部位.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生物化学 生物化学
- 翻译后修改 翻译后修改
背景情况:
- 主细胞因子-1 (HCF-1) 对于调节人类细胞周期进展至关重要.
- 在HCF-1中,蛋白质溶解成熟过程涉及重复序列的分裂.
- 与O结合的N-乙糖胺 (O-GlcNAc) 转移酶 (OGT) 是一个对营养素有反应的酶,参与了这个过程.
研究的目的:
- 为了阐明OGT分裂HCF-1的分子机制.
- 调查OGT和HCF-1之间的相互作用的结构基础.
- 为了确定HCF-1裂变和O-GlcNAc糖化是否发生在同一个活性部位.
主要方法:
- 与HCF-1的OGT四基重复域相互作用的结构分析.
- 生物化学试验研究了HCF-1重复的裂变由OGT.
- 局部定向的突变发生改变HCF-1裂变部位.
主要成果:
- OGT的四基重复域结合了HCF-1重复的碳酸末端.
- HCF-1分裂部位位于OGT活性部位内,靠近尿素二酸盐-GlcNAc结合口袋.
- 在氨酸和谷氨酸残留物之间发生裂变,形成一个氨酸产物.
- 将裂解部位的谷氨酸转化为血清使得HCF-1重复成为糖化基质.
结论:
- HCF-1蛋白质分解裂变和O-GlcNAc蛋白质糖化被OGT在同一活性位点内催化.
- 这一发现提供了HCF-1成熟和O-GlcNAc修饰之间的机制联系.
- 这项研究揭示了OGT活性部位在蛋白质加工中的双重功能.
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