用双极EPR光谱学解决人类抗原输送器Ortholog TmrAB中的合规合和转抑制
Katja Barth1, Susanne Hank2, Philipp E Spindler1
1Institute of Physical and Theoretical Chemistry , Goethe University Frankfurt , Max-von-Laue-Str. 7 , 60438 Frankfurt/Main , Germany.
Journal of the American Chemical Society
|January 9, 2018
概括
这项研究揭示了ATP结合盒 (ABC) 出口物中的不对称核酸结合位 (NBS) 如何调节输送器功能,并解释了基质诱导的抑制. 这些发现为了解医学上重要的载体提供了框架.
科学领域:
- 膜蛋白的生物物理
- 结构生物学
- 生物化学
背景情况:
- 酸结合盒 (ABC) 出口物是涉及运输多种基质的关键膜蛋白.
- 不正常的ABC输出者与各种人类疾病有关.
- 不对称核酸结合点 (NBS) 和基质诱导的抑制在ABC出口者的功能意义尚不清楚.
研究的目的:
- 对ABC出口商的催化不对称性的功能相关性进行调查.
- 阐明基质诱导的转抑制机制.
- 描述TmrAB传送器的结构动态.
主要方法:
- 使用先进的电子双共振 (DEER) 光谱学.
- 这项研究重点是TmrAB,它是人类抗原转位复合体TAP的同源.
- 分析了形态平衡和领域的相互依赖性.
主要成果:
- 在ATP的存在下,TmrAB在向内和向外的形状之间存在着可调节的平衡.
- 这两个NBS在开放到关闭的平衡中表现出显著的不对称性.
- 通过向外转向向封闭状态的反向转变来定义转向抑制.
结论:
- 可逆形态平衡在ABC出口商的功能和监管中发挥着核心作用.
- 在不对称的传送器中建立了跨抑制的机制框架.
- 这项研究证明了在大型膜蛋白复合体中解决平衡群体及其相互依赖的可行性.
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