通过Ycf1的去化调节域进行自抑制的结构基础
Nitesh Kumar Khandelwal1,2, Thomas M Tomasiak3
1Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Nature communications
|March 17, 2024
概括
酵母因子1 (Ycf1) 自抑制是由其调节域 (R域) 介导的. 这项研究揭示了脱的R域的针头结构,揭示了它阻断Ycf1活动的机制.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 酵母因子1 (Ycf1) 是一种ATP结合盒 (ABC) 载体,通过将谷氨和重金属合物隔离到真空中,对细胞解毒至关重要.
- Ycf1的活动由其C子家族特定的调节域 (R域) 调节,该域需要酸化才能激活,并且通过未知的机制在脱化时经历自身抑制.
研究的目的:
- 通过描述R域的脱化状态来阐明Ycf1自身抑制的结构基础.
- 了解R域酸化调节Ycf1转运体活动的机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来捕捉去化Ycf1.1的结构.
- 结构分析的重点是Ycf1基质腔内的非化R域的构造和结合模式.
主要成果:
- 无化R域采用有序的针头拓,在Ycf1基质腔内结合.
- 这种抑制结构与病毒抑制剂和细菌毒素具有相似之处.
- 在R-域发针转内的特定酸化位被确定为对形状变化和Ycf1激活至关重要的.
结论:
- 在无化状态下,R域的发针结构通过占据基质腔位来调解Ycf1的自身抑制.
- 酸化可能通过改变R域的构造来释放这种自身抑制,从而激活载体.
- 这项工作为R-域介导的ABC传递器调节提供了一个结构机制.
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