在人类多药物耐药性中,冷电子显微镜确定ATP结合磁带输送器的结构视图
Wenjie Fan1, Kai Shao1, Min Luo1
1Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
Biomolecules
|February 24, 2024
概括
本综述详细介绍了ATP结合盒 (ABC) 载体的结构和功能,重点关注它们在多药性耐药性 (MDR) 中的作用. 了解这些细胞是开发克服化疗耐药性的新策略的关键.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- ATP结合盒 (ABC) 载体是参与溶液运输的关键膜蛋白.
- 过度表达ABC载体是多药耐药性 (MDR) 的主要机制,限制了癌症和神经系统疾病的治疗疗效.
- 多抗药阻碍药物积累和输送,需要有效逆转策略.
研究的目的:
- 提供临床意义上的人类ABC载体在MDR中涉及的综合性审查.
- 为了比较这些载体的功能机制在多药性耐药性的背景下.
- 突出结构性见解,可以为MDR逆转策略的开发提供信息.
主要方法:
- 文献综述侧重于MDR相关的ABC载体的结构和功能研究.
- 对ABCB1,ABCC1,ABCG2,ABCC3和ABCC4等关键传送器的冷电子显微镜数据的分析.
- 对基质结合,转位机制和抑制剂相互作用的比较分析.
主要成果:
- 低温电子显微镜已经揭示了主要的MDR相关的ABC传送器的详细结构.
- 新的结构信息提高了对基质识别,药物结合部位和传输机制的理解.
- 对抑制剂与ABC载体相互作用的洞察力为药物设计提供了基础.
结论:
- 人类MDR ABC传送器的结构阐明正在迅速推进.
- 了解输送器结构-功能关系对于克服多药性耐药性至关重要.
- 本综述巩固了结构知识,以指导MDR逆转的未来治疗策略.
更多相关视频
12:48Measuring Cation Transport by Na,K- and H,K-ATPase in Xenopus Oocytes by Atomic Absorption Spectrophotometry: An Alternative to Radioisotope Assays
Published on: February 19, 2013
10.6K
08:27Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
Published on: January 7, 2019
9.5K
相关概念视频
01:31ABC Transporters: Exporter
4.3K
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...
4.3K
01:27ABC Transporters: Importer
2.7K
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:
2.7K
01:27ATP Driven Pumps I: An Overview
8.2K
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
8.2K
01:06Carrier-Mediated Transport
426
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
426
01:31Membrane Transporters
11.0K
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...
11.0K
01:44The Significance of Membrane Transport
25.9K
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...
25.9K