人类平衡调节器的结构和封闭机制2
Wooyoung Choi1, Nicolina Clemente1, Weinan Sun2,3
1Van Andel Institute, Grand Rapids, MI, USA.
Nature
|November 29, 2019
概括
平衡调节器 (CALHM) 是参与ATP释放和神经元功能的离子通道. 这项研究揭示了CALHM2通道
科学领域:
- 结构生物学
- 分子神经科学
- 离子通道生理学
背景情况:
- 平衡调节器 (CALHM) 是参与ATP释放和神经元信号的关键离子通道.
- CALHM功能障碍与神经系统疾病有关.
- 了解CALHM2的结构是阐明其功能和功能障碍的关键.
研究的目的:
- 确定人类CALHM2通道的高分辨率结构.
- 阐明红 (RUR) 抑制CALHM2通道的机制.
- 揭示CALHM2通道的架构和封闭原则.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得CALHM2的结构.
- 对于没有Ca2+的活性状态和与RUR结合的抑制状态,都确定了结构.
- 在RUR结合时分析通道架构,对称性和形状变化.
主要成果:
- 在活性和抑制状态下获得人类CALHM2的高分辨率冷EM结构.
- CALHM2通道形成无半通道和间隙结.
- 红结合会诱导形状变化,包括收缩的孔隙和升起的S1螺旋,稳定抑制状态.
结论:
- 这项研究提供了CALHM2通道架构和对称性的详细结构见解.
- 建议采用S1和N终端螺旋体的双截门机制.
- 在S1附近的RUR结合部位解释了通道抑制,为了解健康和疾病中的CALHM2通道功能提供了基础.
更多相关视频
相关概念视频
Calmodulin-dependent Signaling
5.9K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.9K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.6K
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...
3.6K
Feedback Regulation of Calcium Concentration
3.9K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.9K
G-Protein Gated Ion Channels
5.5K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
5.5K
Skeleton and Calcium Homeostasis
5.6K
Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
5.6K
Mechanically-gated Ion Channels
7.5K
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...
7.5K


