对CmABCB1基板运输结构和能量分析
Kei Moritsugu1,2, Ryuji Ishida2, Takumi Someya2
1Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
Journal of chemical theory and computation
|October 4, 2025
概括
这项研究揭示了P-glycoprotein (P-gp) 如何使用自由能景观运输分子. ATP结合驱动着形状变化,促进基质释放和细胞流动.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物物理学 分子生物物理学
背景情况:
- 作为ABCB1载体的P-glycoprotein (P-gp) 通过形状变化排出疏水性化合物.
- 其同类物 (CmABCB1) 的晶体结构表明,运输涉及跨膜螺旋 (TMH) 和核酸结合域 (NBD) 的运动.
研究的目的:
- 计算P-gp向内转向 (IF) 到向外转向 (OF) 的最小自由能量路径 (MFEP).
- 使用晶体学数据阐明罗达胺6G (R6G) 运输的结构和能量基础.
主要方法:
- 使用字符串方法计算IF-to-OF合规过渡的MFEP.
- 分析了ATP结合,NBD二元化和基质相互作用的作用.
主要成果:
- ATP结合和NBD二元化克服了能量障碍,破坏了芳香性疏水网络 (AHN).
- 这促进了基质的结合,并导致了中间基质封闭 (Occ) 状态.
- 基质相互作用破坏了Occ状态的稳定,通过TMH运动促进过渡到OF形状.
结论:
- 基于MFEP的自由能量景观有效地揭示了膜载体分子机制.
- 该研究详细介绍了P-gp介导基质运输的逐步过程.
更多相关视频
13:16Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
9.7K
06:47Author Spotlight: A Bicelle Crystallization Setup for ABC Transporter Membrane Proteins to Advance Drug Development
Published on: August 25, 2023
1.8K
相关概念视频
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
137.0K
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...
137.0K
ABC Transporters: Importer
3.4K
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
3.4K
ABC Transporters: Exporter
6.3K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
6.3K
The ADP/ATP Carrier Protein
4.1K
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
4.1K
Drug Absorption Mechanism: Carrier-Mediated Membrane Transport
5.8K
Certain large, lipid-insoluble drug molecules that resemble amino acids, peptides, or glucose, require specialized carrier proteins to facilitate their diffusion across cell membranes. This transport can occur through either facilitated diffusion, which does not require energy input, or active transport, which does require energy input.
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
5.8K
