在P2X受体中,ATP结合和离子通道激活的分子机制
Motoyuki Hattori1, Eric Gouaux
1Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Nature
|April 27, 2012
概括
研究人员揭示了斑马鱼P2X4受体的结构,详细介绍了ATP结合部位和开放的离子通道孔. 这为药物开发的ATP依赖离子通道封锁机制提供了关键的见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- P2X受体是三元ATP带离子通道,对各种生理过程至关重要.
- 了解它们的结构,特别是ATP结合部位和门机制,对于药理学至关重要.
研究的目的:
- 为了确定斑马鱼P2X4受体的三维结构.
- 阐明依赖ATP的离子通道关的结构机制.
- 描述开放的离子通道孔的结构.
主要方法:
- 使用X射线结晶学来获得斑马鱼P2X4受体的结构.
- 对阿波受体和与ATP复合的受体都确定了结构.
主要成果:
- 斑马鱼P2X4受体与ATP复合的晶体结构揭示了一个新的ATP结合动机和一个开放的离子通道孔.
- ATP结合会诱导形状变化,包括裂关闭和细胞外前庭的辐射扩张.
- 离子通道孔的开放与前庭通过跨膜螺旋扩张扩大.
结论:
- 这项研究为P2X4受体的ATP结合部位和开放离子通道孔提供了第一个结构性见解.
- 这些发现阐明了依赖ATP的离子通道封闭的机制.
- 这些结构信息将促进开发针对P2X受体的新型药理学药剂.
相关概念视频
ATP Driven Pumps I: An Overview
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 are...
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 are...
ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...


