在B12-贩运途径中的一个蛋白间Co-S协调复合体
Zhu Li1, Romila Mascarenhas1, Umar T Twahir2
1Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600, United States.
Journal of the American Chemical Society
|September 2, 2020
概括
在CblD的陪伴者捐赠一个硫联体到cob(II) 胺,形成一个独特的蛋白间复合物与CblC. 这种相互作用对于细胞内可巴拉明贩运和辅因子转移至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 科巴胺 (维生素B12) 对于许多代谢过程至关重要.
- CblC和CblD是参与细胞内可巴胺贩运的陪伴者.
- 在这种途径中CblD的确切作用在很大程度上是未知的.
研究的目的:
- 阐明CblD陪伴者在可巴胺走私途径中的功能.
- 描述CblC和CblD之间的相互作用.
- 了解涉及CblD的可巴拉明加工机制.
主要方法:
- 氨酸扫描突变发生,以识别硫供体残留物.
- 电子磁共振 (EPR) 谱学用于研究可巴拉胺中间体.
- 用X射线吸收光谱 (XAS) 来分析蛋白质间的-硫键.
- 进行X射线晶体学以可视化复杂的结构.
主要成果:
- CblD提供了一种硫连接体给 cob (II) 胺,结合到 CblC.
- 在CblD上的素-261 (Cys-261) 被确定为硫供体.
- 形成了一种不寻常的蛋白质间-硫 (Co-S) 键,导致了硫酸- (III) 胺.
- 晶体结构显示了人类的CblD-thiolato-cob (III) 胺复合体.
结论:
- CblD充当硫供体,通过蛋白间协调复合体促进可巴拉明的加工.
- 这种机制突出了用于辅因子转移的协调化学的利用.
- 这些发现提供了对可巴拉明走私途径的关键见解.
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