内生菌体MCE脂质输送物的结构
James Chen1, Alice Fruhauf1, Catherine Fan1
1Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
Nature
|July 26, 2023
概括
结核菌需要吸收营养来产生毒性. 研究人员阐明了Mce1的脂质进口机器结构,揭示了其组装和跨越菌根细胞外的脂质运输的新途径.
科学领域:
- 微生物学
- 结构生物学
- 生物化学
背景情况:
- 结核菌在巨细胞中吸收宿主营养以获得毒性和生存.
- 哺乳动物细胞进入 (MCE) 蛋白质是重要的毒性因子,参与了脂肪酸和胆固醇在真菌细胞外中运输.
- 在货物运输中MCE蛋白质复合物的组装和功能在很大程度上是未知的.
研究的目的:
- 确定Mycobacterium smegmatis的Mce1脂质进口机的结构.
- 阐明MCE蛋白在脂质运输中的组装机制.
- 通过菌根细胞外提出一种MCE介导的脂质进口模型.
主要方法:
- 用冷电子显微镜 (cryo-EM) 确定Mce1复合物的结构.
- 通过AlphaFold2预测识别MCE复杂子单元.
- 生物化学分析以了解脂质运输机制.
主要成果:
- Mce1复合体的冷EM结构揭示了跨越细胞外的长长的ABC输送器.
- 鉴定出一种新的,曲的,针状的域,形成一种受保护的疏水路径,用于脂质的运输.
- 在Mce1复合体内发现了一个新的子单元LucB.
结论:
- Mce1复合体组装成一个完整的脂质进口机器,能够跨越菌根细胞外.
- 鉴定到的结构为MCE介导的脂质运输机制提供了洞察力.
- 这项研究提供了在菌根细胞外中输入脂质的结构模型,这对M.结核病的发病至关重要.
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