结构定位揭示了IP3受体的Ca2+依赖性构造格局
Navid Paknejad1,2, Vinay Sapuru1,2, Richard K Hite3
1Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Nature communications
|October 29, 2023
概括
伊诺西1,4,5-三酸盐受体 (IP3Rs) 控制的振荡. 新的研究表明,结合不会改变IP3R结构,而是影响其构造状态,解释信号.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
背景情况:
- 伊诺西1,4,5-三酸盐受体 (IP3Rs) 是细胞内膜网膜中至关重要的通道.
- 它们的活动通过振荡调节了细胞中的重要过程,如受精,细胞分裂和细胞死亡.
- 推动这些振荡的IP3R双相依赖的结构基础仍然不太清楚.
研究的目的:
- 阐明IP3Rs的双相依赖的基础结构机制.
- 了解不同度如何调节IP3R通道活动和形态状态.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于捕捉IP3R结构在广泛的度 (五个数量级) 的范围.
- 使用无偏图像分析来分析受体的构造格局.
- 粒子计数被用作相对构成自由能量的代理值.
主要成果:
- 结合不会诱导明确的形状变化,而是将受体偏向于复杂景观中的特定状态.
- IP3Rs在高亲和位点结合后从低能量的静止状态通过预激活状态过渡到激活状态.
- 在高度下,IP3Rs有利于通过第二个低亲和度结合点稳定抑制状态.
结论:
- 这项研究为IP3R活性对双相的依赖提供了机制性的解释.
- 结合作为构造组合的调节器而不是离散结构变化的诱导剂.
- 这项工作加深了我们对信号及其IP3Rs调节的理解.
相关概念视频
Calmodulin-dependent Signaling
5.2K
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,...
5.2K
Feedback Regulation of Calcium Concentration
3.4K
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...
3.4K
IP3/DAG Signaling Pathway
12.1K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.1K
Phosphoinositides and PIPs
8.6K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.6K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
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...
2.3K


