一个MATE传送器的亲和性定向基板/H+-反端口
Koh Takeuchi1, Takumi Ueda2, Misaki Imai3
1Graduate School of Pharmacological Sciences, The University of Tokyo, Hongo, Bunkyo, Tokyo 113-0033, Japan; Molecular Profiling Research Center for Drug Discovery and Cellular Molecular Biotechnology Research Institute, National Institute of Advanced Science and Technology, Aomi, Koto, Tokyo 135-0063, Japan.
Structure (London, England : 1993)
|May 30, 2024
概括
多种药物和毒素挤出 (MATE) 载体使用离子梯度驱逐毒素. 这项研究揭示了MATE传送器通过一种亲和性导向的机制运行,将合基板与质子运动结合,以有效排泄.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 膜运输 运输 膜运输
背景情况:
- 多种药物和毒素挤出 (MATE) 载体对于细胞解毒至关重要.
- 虽然存在MATE传送器结构,但基质出口与离子流入相结合的机制尚不清楚.
研究的目的:
- 为了阐明MATE家族运输器的运输机制.
- 研究Pyrococcus furiosus MATE (PfMATE) 的结构动力学和基质结合.
主要方法:
- 解决方案核磁共振 (NMR) 光谱法的PfMATE.
- 酸性残留的局部定向突变发生,以探测质子状态和形状变化.
主要成果:
- PfMATE存在于面向内 (IF) 和面向外 (OF) 形状之间的平衡状态,由Glu163质子调节.
- 基质识别发生在质子化IF形状中的中μM亲和度.
- OF构造表现出弱的mM基底亲和力,促进细胞外释放.
结论:
- pfMATE作为一种以亲和力为导向的H+/基质抗载体而起作用.
- 对于高亲缘关系基质结合,IF形状的质子化是必不可少的.
- 随后的质子释放驱动H+合基质分泌,阐明了MATE运输机制.
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