基质和产品复合体揭示了HHAT对虫化的机制
Yiyang Jiang1, Thomas L Benz1, Stephen B Long2
1Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Science (New York, N.Y.)
|June 11, 2021
概括
刺酸转移酶 (HHAT) 修改刺蛋白质用于信号和癌症的发展. 结构洞察力揭示了HHAT在细胞膜中的功能,为新的癌症药物开发提供了潜力.
科学领域:
- 生物化学
- 结构生物学
- 分子生物学
背景情况:
- 子蛋白对动物发育至关重要,
- 转化后的修饰,特别是由 Hedgehog acyltransferase (HHAT) 进行的氨基末端棕化,对于 Hedgehog 蛋白的功能至关重要.
- 了解 HHAT 的机制对于破译 Hedgehog 信号通路及其在癌症发生中的作用至关重要.
研究的目的:
- 通过HAT阐明刺蛋白棕化结构和机制的基础.
- 提供高分辨率的结构见解HAT基质复合物和催化过程.
- 探索这些发现对相关的化酶和癌症疗法的影响.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定人类HAT的结构.
- 获得了HHAT与其棕甲酶基质和棕甲虫的复合结构.
- 高分辨率数据 (2.7和3.2安格斯特罗姆) 使得详细的原子级分析成为可能.
主要成果:
- 确定了人类HAT的高分辨率冷EM结构,揭示了它与基质的相互作用.
- 这些结构说明了HAT如何通过在其活性部位内将膜相关基质聚集在一起来促进催化.
- 阐明了HHAT的功能机制,强调了其独特的基质参与方法.
结论:
- 确定的结构为HAT对虫蛋白棕化机制提供了前所未有的洞察力.
- 这些发现揭示了HHAT如何克服在嵌入膜的活性部位内容纳具有不同特性的基质的挑战.
- 对HAT的结构和机制的理解可能为开发向癌症抑制剂铺平道路.
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