运输和抑制人类葡萄糖-6-酸盐运输体G6PT的结构基础
Zhanyi Xia1,2, Yaqi Wang3, Di Wu1,2
1Beijing National Laboratory for Condensed Matter Physics, Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.
Nature communications
|October 24, 2025
概括
人类的葡萄糖-6-酸盐转运体 (G6PT) 结构由冷EM揭示,显示它如何结合葡萄糖-6-酸盐 (G6P) 并被基酸 (CHA) 抑制. 这为G6PT功能和糖原储存疾病1b.提供了洞察力.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 人类的葡萄糖-6-酸盐运输体 (G6PT) 对葡萄糖平衡至关重要,其功能障碍导致糖原储存疾病1b.
- 包括基质识别和抑制在内的G6PT功能的结构基础在很大程度上是未知的.
研究的目的:
- 为了阐明各种状态的人类G6PT的冷电子显微镜 (cryo-EM) 结构.
- 了解G6P结合和酸 (CHA) 抑制的分子机制.
- 调查G6PT和葡萄糖-6-酸酶 (G6PC) 之间的关系.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定人类G6PT的结构.
- 生物化学测试以评估G6PT活性和相互作用.
主要成果:
- 该研究报告了人体G6PT的apo,G6P结合和CHA结合形式的冷-EM结构.
- G6P结合部位由酸盐和葡萄糖部分的不同的子部位组成.
- 酸 (CHA) 与G6P部位结合,使G6PT稳定在部分封闭的形状中,并抑制其活性.
- 通过与G6PC共同表达,G6PT活性得到增强,但它们不形成复合体.
结论:
- 确定的结构为G6PT的传输机制和CHA.的抑制提供了详细的了解.
- 这些发现为探索G6PT结构功能关系和G6PT相关疾病的病理学提供了结构基础.
- 这项研究为开发针对G6PT相关疾病的向疗法开辟了道路.
更多相关视频
相关概念视频
Glucose Transporters
27.2K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
27.2K
Secondary Active Transport
9.3K
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...
9.3K
Secondary Active Transport
136.9K
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...
136.9K
Membrane Proteins
29.2K
Plasma membranes have integral transmembrane proteins involved in facilitated transport. These proteins are collectively referred to as transport proteins, and they function as either channels for the material or as carriers themselves. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids and a hydrophilic channel through their core that provides a hydrated opening for solutes to pass through the membrane layers. Passage through the channel allows...
29.2K
Glucose Absorption Into the Small Intestine
35.0K
Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
35.0K
The Significance of Membrane Transport
41.0K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
41.0K


