在L型Ca2+通道中的Ca2+选择性和离子透的分子决定因素
J Yang1, P T Ellinor, W A Sather
1Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, California 94305.
Nature
|November 11, 1993
概括
这项研究表明,通道中的四个关键的谷氨酸残留物对于高亲和度离子结合至关重要. 修改表明这些残留物对的选择性和透性至关重要,影响细胞信号传输.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 细胞生理学 细胞生理学
背景情况:
- 电压通道控制细胞的流入,对各种细胞反应至关重要.
- 这些通道对离子 (Ca2+) 具有选择性,而不是 (Na+) 和 (K+) 离子.
- 假设通道孔中的四个保存的谷氨酸残留物能够调节Ca2+结合.
研究的目的:
- 系统地研究在Ca2+通道孔中四种保存的谷氨酸残留物的作用.
- 确定每个谷氨酸酸对高亲和度Ca2+结合和离子选择性的贡献.
- 改进Ca2+通过电压通道透的现有模型.
主要方法:
- 位点导向的突变发生,在四个关键的谷氨酸位点中创建单个氨基酸替代.
- 电生理学记录以评估突变对Ca2+和Cd2+结合的影响.
- 对Ca2+块的分析,以评估个别残留物对离子结合亲和力的贡献.
主要成果:
- 发现所有四种谷氨酸残留物都参与了Ca2+和Cd2+的高亲和结合.
- 每个谷氨酸都对离子结合有明显的贡献,重复III中的残留物显示出最显著的效果.
- 在特定的谷氨酸位点对氨酸的突变取消了微分子Ca2+阻断,表明它们的重要作用.
结论:
- 目前的Ca2+透模型需要修改,以包括两个Ca2+离子在四个谷氨酸残留物附近的结合.
- 这些谷氨酸酸的功能不平等可能会促进多个Ca2+离子同时结合,这些离子在单个档中移动.
- 2+离子之间的离子竞争和静电排斥可能有助于快速的道流速.
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