一种真菌ABC转运体调解了水友性化合物的吸收
S Rempel1,2, C Gati3,4, M Nijland1
1Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
Nature
|April 17, 2020
概括
结核菌使用Rv1819c来运输维生素B12 (胺),尽管它的出口结构. 这一发现揭示了Rv1819c是结核病发病的关键多溶质载体.
科学领域:
- 微生物学
- 结构生物学
- 生物化学
背景情况:
- 结核菌 (Mtb) 引起结核病,并且可以合成维生素B12 (可巴胺),但可巴胺的摄取与致病性有关.
- Mtb缺乏特征性可巴胺转运体,但Rv1819c对于可巴胺吸收至关重要,尽管它预测的ATP结合盒 (ABC) 出口折叠.
研究的目的:
- 阐明Mycobacterium结核病中的Rv1819c蛋白的结构和功能.
- 调和有关Rv1819c在胺运输中的作用和其作为ABC出口商的结构预测的相互矛盾的证据.
主要方法:
- 用X射线结晶学来确定Rv1819c的3D结构.
- 对Rv1819c氨基酸序列和结构特征的生物信息分析.
- 功能性测试以评估Rv1819c对可巴胺和白素的运输能力.
主要成果:
- 这些结构证实Rv1819c具有ABC输出折叠.
- 在Rv1819c中发现了一个充满水的大洞 (7,700 Å3),方便运输.
- Rv1819c 能够携带胺和白胺,这两种结构上是不同的水友化合物.
结论:
- Rv1819c作为水友分子的多溶液输送器.
- 这种传输器类似于ABC传输器家族中的多种药物输出器.
- Rv1819c的双重传输能力对了解结核病原和潜在的治疗策略有影响.
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