氨酸受体的架构和形状开关机制
Rouslan G Efremov1, Alexander Leitner2, Ruedi Aebersold3
11] Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), 1050 Brussels, Belgium [3] Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium.
Nature
|December 4, 2014
概括
瑞诺丁受体 (RyRs) 通过释放来控制肌肉收缩. 这项研究揭示了RyR1通道.
科学领域:
- 生物物理学的生物物理.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 肌肉收缩依赖于通过氨酸受体 (RyRs) 从质网膜释放的 (Ca2+).
- 虽然 RyRs 是大型的同质干通道,与人类疾病有关,但它们的复杂调节仍然不太清楚.
- 了解 RyR 结构对于阐明肌肉功能和疾病机制至关重要.
研究的目的:
- 为了确定子氨酸受体1 (RyR1) 的高分辨率架构.
- 阐明RyR1调节和功能的结构基础.
- 为了解 RyR 相关疾病背后的分子机制提供见解.
主要方法:
- 使用电子冷显微镜 (cryo-EM) 解析了子RyR1.1.的结构.
- 进行了高分辨率的结构分析,以确定关键领域及其布局.
- 研究了已识别的结构特征的功能影响.
主要成果:
- 子RyR1的冷-EM结构在6.1 Å分辨率下确定.
- RyR1的细胞质区域包括大型α-solenoid域和参与蛋白质相互作用的较小域.
- 跨膜域表现出一个模拟结构,整合了和pH受阻离子通道的特征.
- 确定了结合的EF-hand域,并表明它可以作为通道活性的一种全osteric gate.
结论:
- 确定的架构提供了RyR1.1.的详细分子蓝图.
- 这些结构洞察力解释了RyR1的复杂调节及其作为通道的作用.
- 这项工作为了解疾病中的RyR突变和开发向治疗奠定了基础.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
5.1K
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...
5.1K
The Two-State Receptor Model
3.6K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
3.6K
Antihypertensive Drugs: Action of Calcium Channel Blockers
2.4K
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
2.4K
Mechanically-gated Ion Channels
8.2K
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...
8.2K
Mechanically-gated Ion Channels
5.9K
5.9K
Cross-bridge Cycle
125.8K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
125.8K


