丝状结构揭示了人类乙-CoA碳氧酶的动态组织
Fayang Zhou1,2,3,4, Yuanyuan Zhang1,2,3, Yuyao Zhu2,4
1College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Science advances
|October 9, 2024
概括
研究人员使用冷EM揭示了人类乙-CoA碳氧酶 (ACC) 的结构动态. 不活跃的ACC1形成细丝,而激活则揭示了对脂肪酸合成调节的洞察力.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 人类乙-CoA碳氧酶 (ACCs) 是关键的酶,催化脂肪酸合成的速度限制步骤.
- 控制ACC动态组织和调节的分子机制在很大程度上仍未被阐明.
研究的目的:
- 确定人类ACC1调节和动态组织的结构基础.
- 阐明在脂肪酸代谢中的ACC激活和功能背后的分子机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定人类ACC1.1的结构.
- 在与乙-A复合体中的非活性ACC1和在脱化和酸盐处理后激活的ACC1的结构得到了解决.
主要成果:
- 不活跃的人类ACC1在乙-CoA的存在下形成了一个独特的丝状结构.
- 激活ACC1的冷电磁结构在2.55 Å分辨率下确定.
- 观察到生物素结合与乙-CoA结合部位相距很远,而没有乙-CoA,这表明了潜在的协调.
结论:
- 这项研究为人类ACC的结构动态和调控机制提供了新的见解.
- 这些发现揭示了ACC1如何在不活跃状态和活跃状态之间过渡,影响脂肪酸合成.
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