非对称的连接键促进了 pentameric 连接键门离子通道中的构造过渡
David Mowrey1, Mary Hongying Cheng, Lu Tian Liu
1Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Journal of the American Chemical Society
|January 24, 2013
概括
普罗波与GLIC通道的不对称结合,而不是对称结合,导致通道关闭. 这种在结合部位的对称性打破通过改变通道形状来驱动功能抑制.
科学领域:
- 生物物理学的生物物理.
- 分子药理学分子药理学
- 计算生物学 计算生物学
背景情况:
- 普罗波是一种麻醉剂,可以抑制GLIC离子通道.
- 晶体结构显示propofol与GLIC结合在一个开放通道的形状,创造了一个悖论.
研究的目的:
- 研究波结合对称性如何影响GLIC通道形状.
- 确定普罗波对GLIC的抑制作用背后的机制.
主要方法:
- 在GLIC上进行了1.5μs的分子动力学模拟,使用不同的propofol占用率 (0,1,2,3,5).
- 在对称和不对称的结合条件下分析了通道构造,水化和TM2螺旋运动.
主要成果:
- 对称的propofol结合 (0或5个分子) 保持了一个开放通道形状.
- 不对称的结合 (1,2,或3个分子) 加快了脱水,并促进了封闭通道形状.
- 不对称的结合导致了道内的形状异质性和不平衡力的增加.
结论:
- 不对称的普罗波结合是GLIC功能抑制的可能原因.
- 连接体结合点中的对称性破裂在促进离子通道构造转换方面发挥着至关重要的作用.
相关概念视频
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
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...
Three Subfamilies of Ligand-gated Ion Channels
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...
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
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...
Three Subfamilies of Ligand-gated Ion Channels
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...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...


