在K(+) 道中,激活门和失活门之间的合的结构基础
Luis G Cuello1, Vishwanath Jogini, D Marien Cortes
1Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
Nature
|July 9, 2010
概括
K(+) 通道激活和非激活之间的相互作用是由Phe 103侧链运动机械驱动的. 这些运动会破坏选择性过器的稳定性,导致通道不活化并影响门动力学.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 分子生理学分子生理学
背景情况:
- (K(+)) 通道对于细胞电信号传输至关重要.
- 合激活和非激活门是K(+) 通道的关键功能性质.
- 之前的研究表明,通过离子效应和氨酸可访问性来证明合.
研究的目的:
- 阐明连接K(+) 通道激活和非激活的结构机制.
- 为了确定特定的残留物和运动,负责触发失活.
- 为了调查Phe 103在KcsA通道关中的作用.
主要方法:
- 在各种开放状态下分析多个KcsA晶体结构.
- 分子动力学模拟用于计算相互作用能量.
- 位点定向的突变发生 (F103A,F103C,F103W) 来评估功能性影响.
- 与Shaker K(+) 通道突变物 (I470A) 的比较.
主要成果:
- 内束门的运动,特别是TM2螺旋旋转,导致Phe 103倾斜.
- 佩103倾斜通过与孔螺旋和邻近残留物的相互作用来破坏选择性过器的稳定性.
- 在位置103的突变对无活化动力学产生了大小依赖的影响.
- 分子动力学证实了Phe 103与开放状态的周围残留物之间有利的相互作用.
结论:
- 在KcsA中,Phe 103侧链重新排列机械配对激活和非激活.
- 这种机制可能扩展到其他K(+) 频道家族.
- 体合依赖于通过体接触传播的机械变形.
相关概念视频
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Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
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