通过calmodulin调节心脏瑞诺丁受体2
Deshun Gong1, Ximin Chi2, Jinhong Wei3
1Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. gds13@tsinghua.org.cn.
Nature
|July 7, 2019
概括
卡尔莫杜林 (CaM) 与RyR2通道的结合取决于Ca2+水平. 这种依赖Ca2+的CaM结合改变了RyR2的结构,影响了心肌刺激-收缩的合.
科学领域:
- 结构生物学 结构生物学
- 分子心脏病学分子心脏病学
- 离子通道规则 离子通道规则
背景情况:
- 氨酸受体2 (RyR2) 是一个关键的高导电性细胞内通道.
- RyR2 在心肌中调解激发-收缩合.
- 卡尔莫杜林 (CaM) 是已知的RyR2活性的Ca2+依赖调节器.
研究的目的:
- 为了阐明由CaM调制RyR2的结构机制.
- 了解Ca2+依赖的CaM结合如何影响RyR2通道关口.
主要方法:
- 在八种不同的条件下确定了猪RyR2与人类CaM复合的结构.
- 使用冷电子显微镜 (cryo-EM) 或X射线晶体学进行结构确定.
主要成果:
- 在RyR2上为apo-CaM和Ca2+-CaM确定了不同的但重叠的结合点.
- 证明了与CaM结合的Ca2+,而不是RyR2,决定了CaM结合部位的转移.
- 观察到Ca2+-CaM诱导的结构变化,导致特定RyR2激活状态的孔密闭 (PCB95,Ca2+-激活).
结论:
- 2+-M结合会诱导RyR2中心域的显著构造变化,导致孔隙关闭.
- 在ATP,咖啡因和Ca2+激活下,RyR2的孔隙保持开放,即使存在Ca2+-CaM.
- Ca2+-CaM 作为影响 RyR2 通道关口动态的多个竞争调节器之一.
相关概念视频
Calmodulin-dependent Signaling
6.0K
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,...
6.0K
Internal Receptors
74.3K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.3K
Receptor-mediated Endocytosis
110.6K
Overview
110.6K
Enzyme-linked Receptors
86.2K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.2K
G-protein Coupled Receptors
131.7K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.7K
Types of Receptors: Internal Receptors
31.6K
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
31.6K


