神经递质/同载体正体 LeuT 具有单个高亲和度基质位点
Chayne L Piscitelli1, Harini Krishnamurthy, Eric Gouaux
1Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Nature
|December 24, 2010
概括
神经递质/同载体 (NSS) 对于突触功能至关重要. 这项研究明确表明,LeuT只有一个高亲和度结合位点,反驳了两个全结合位点的模型.
科学领域:
- 神经科学是一个神经科学.
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 神经递质/同载体 (NSS) 是重要的膜蛋白,负责在化学突触中重新吸收神经递质.
- NSS与神经系统疾病有关,并且是各种药物的点.
- 作为一种 prokaryotic NSS 的 LeuT,可以作为理解 NSS 结构-功能关系的模型.
研究的目的:
- 解决关于 LeuT 传送器中高亲和度基质结合位数的争议.
- 调查LeuT.中的两个假定结合点 (S1和S2) 之间的拟议的全结合.
主要方法:
- 使用异热定位热量计,平衡透析和闪光近距离测试,直接测量基质结合.
- 吸收实验分析基质流动动力学.
- 使用野生型LeuT和S2位点突变物进行比较分析.
主要成果:
- 实验数据证实,LeuT.中存在一个单一的,位于中心的,高亲和度的基质结合部位 (S1).
- 没有证据证明存在第二个高亲和度结合位点 (S2) 或S1和S2之间的全结合.
- 运输动力学是由一个简单的单基板机制准确地描述的.
结论:
- LeuT只有一个高亲和度基质结合点.
- 建议在LeuT中有两个全结合的结合点的模型没有得到实验证据的支持.
- 这一发现澄清了NSS运输的机制,对理解相关的人类运输器有意义.
相关概念视频
Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
Primary Active Transport
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Primary Active Transport
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they...
Membrane Transporters
Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...


