在一个Na+合的神经递质转运器同类物体中,基质调节的门动态
Yongfang Zhao1, Daniel S Terry, Lei Shi
1Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.
Nature
|April 26, 2011
概括
神经递质共导体使用Na(+) 梯度来重新捕获神经递质. 在细胞外部的基质结合控制了细胞内门的开放,提高了运输效率,并揭示了隐藏的NSS运输机制.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 神经递质/Na(+) 配送体 (NSSs) 通过通过Na(+) 共同传输来重新捕获神经递质来终止神经元信号传递.
- 多巴胺,血清素和上腺素的关键NSS是精神兴奋剂和抗抑郁药的目标.
- Prokaryotic NSS 同类 LeuT 的晶体结构揭示了封闭和向外开放的构造,指导功能机制研究.
研究的目的:
- 为了研究基质结合如何与结构转换在LeuT在Na(+) 合运输.
- 阐明细胞外基质结合在控制细胞内门动态和运输效率方面的作用.
主要方法:
- 利用氨酸,一种运输速度比氨酸快10倍的基质,探讨运输动力学.
- 使用先进的成像技术观察了LeuT的细胞内区域的氨酸诱导的动态.
- 研究了初级 (S1) 和二级 (S2) 细胞外结合位点之间的基质结合合作性.
主要成果:
- 细胞外侧的基质结合有助于细胞内门的打开和基质的释放.
- 细胞内门中的氨酸诱导的动态与运输效率直接相关.
- 确定了在S1和S2位点的合作基质结合,控制了超过30年的细胞内门.
结论:
- 揭示了NSS运输机制的功能相关,以前隐藏的方面.
- 强调了细胞外前庭中的第二基质 (S2) 结合部位的关键作用.
- 经过证明的合作结合控制了细胞内关,使得Na(+) 的梯度驱动运输成为可能.
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