在HLA类I结合上扩展O-GlcNAc
Fabio Marino1,2, Marshall Bern3, Geert P M Mommen1,2,4
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Journal of the American Chemical Society
|August 18, 2015
概括
研究人员在人类白细胞抗原 (HLA) I类上发现了意想不到的糖化. 这些扩展的O- 链接N- 乙糖胺 (O- GlcNAc) 修饰在HLA上可能是免疫监测的关键目标.
科学领域:
- 免疫学
- 葡萄糖生物学
- 质谱学
背景情况:
- 人类白细胞抗原 (HLA) 一类分子向T细胞呈现,对免疫监测至关重要.
- 糖化,即糖的添加,通常发生在内网和戈尔吉器官中的蛋白质上.
- 链糖化是一种常见的翻译后修饰,但它对HLA结合的作用尚不清楚.
研究的目的:
- 调查糖化HLA类I结合的意外质谱观测.
- 描述这些糖化酶的性质和起源.
- 探索这些改性的潜在免疫性.
主要方法:
- 质谱测试用于和糖分析.
- 通过分子建模来理解结构含义.
- 在体外酶测试以确认糖转移酶活性.
- 氧离子模式分析以阐明糖结构.
主要成果:
- 在HLA类I上识别O结合的甘氨酸,超出典型的终端修饰.
- 建议这些甘氨酸是扩展的O-N-乙糖胺 (O-GlcNAc) 结构,而不是GalNAc启动.
- 从膜蛋白中获得的O和N结合糖的自然HLAI类呈现的第一份报告.
- 观察到 HLA I 类上位于中心的寡糖可以具有免疫性.
结论:
- HLA I类可以经历复杂的O-GlcNAc糖化,因为它们通过糖化竞争的细胞区进行运输.
- 这些糖化HLA,特别是具有中心寡糖的,是免疫监测的潜在目标.
- 这一发现扩大了对HLA分子的翻译后修改及其对免疫的影响的理解.
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