一个真核寡糖转移酶复合物的原子结构
Lin Bai1, Tong Wang2, Gongpu Zhao3
1Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, USA.
Nature
|February 22, 2018
概括
研究人员揭示了对蛋白质N-糖化至关重要的寡糖转移酶 (OST) 复合物的结构. 这一发现揭示了同翻译性修改过程,并可能有助于开发向抑制剂.
科学领域:
- 结构生物学
- 分子生物学
- 生物化学
背景情况:
- N-糖化是一种关键的翻译后修饰,影响约90%的真核糖蛋白.
- 位于内细胞网中的寡糖转移酶 (OST) 综合体催化了这一重要过程.
- 有限的高分辨率结构数据阻碍了对真核蛋白N-糖化机制的深入理解.
研究的目的:
- 确定Saccharomyces cerevisiae OST复合物的高分辨率结构.
- 阐明同翻译蛋白N-糖化过程的结构基础.
- 提供针对N- 糖化作用的小分子抑制剂的潜在开发见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来实现OST复合物的3.5 Å分辨率结构.
- 确定的结构包括包括Ost1-Ost5,Stt3,Wbp1和Swp1的关键子单位.
主要成果:
- 冷电磁结构揭示了OST复合体及其组成子单位的详细结构.
- 七种脂被确定为该复合体内的子单元间相互作用的媒介.
- 观察到Stt3 N- glycan在ER光线中与Wbp1和Swp1发生相互作用.
- 发现Ost3子单元与Sec61转位子相互作用,引导新生到催化部位.
结论:
- 这种高分辨率结构为同译蛋白N-糖化机制提供了前所未有的洞察力.
- 了解OST复杂结构及其相互作用可能为针对糖化途径的新疗法铺平道路.
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