直接调节酸4,5-双酸基组组的形成和识别
Eva Bilkova1,2, Roman Pleskot3,4, Sami Rissanen5
1Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Technische Universität Dresden , Fetscher Strasse 74, 01307 Dresden, Germany.
Journal of the American Chemical Society
|February 9, 2017
概括
离子 (Ca2+) 直接与酸4,5-双酸 (PI(4,5) P2结合,改变其构型,并阻断其被关键信号蛋白 (如PLC δ1-PH) 识别.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 生物物理学的生物物理.
背景情况:
- 酸,特别是酸4,5-双酸 (PI(4,5) P2,对于细胞过程至关重要.
- 已知离子 (Ca2+) 影响PI (4,5) P2聚类,但其分子机制尚不清楚.
- 了解Ca2+-PI的相互作用是解读细胞信号通路的关键.
研究的目的:
- 调查Ca2+和PI4,5P2之间的直接分子相互作用.
- 阐明Ca2+结合如何影响PI,4,5P2形状及其被蛋白质识别.
- 探索这些相互作用在细胞信号传输中的作用.
主要方法:
- 测量PI(4,5) P2含有脂质体的电动力学潜力.
- 生物化学试验使用脂酶C三角形1斑素同质域 (PLC δ1-PH).
- 振动总频谱学和原子分子动力学模拟.
主要成果:
- Ca2+显著降低PI,4,5P2脂质体的泽塔潜力,表明表面电荷发生了变化.
- 2+完全抑制了PLC δ1-PH对PI的识别,而Mg2+的影响很小.
- 谱学和模拟显示,Ca2+结合诱导PI,4,5P2头组和碳基区域的构造变化.
结论:
- 与PI结合的Ca2+改变了其构造,阻断了与特定的脂质结合域的相互作用.
- 由Ca2+调节的PI{4,5) P2的可切换的构造状态,可能代表了控制细胞信号的新机制.
- 这项研究提供了分子洞察力,了解离子是如何调节酸中介细胞过程的.
更多相关视频
相关概念视频
Phosphoinositides and PIPs
10.4K
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...
10.4K
IP3/DAG Signaling Pathway
15.4K
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...
15.4K
Calmodulin-dependent Signaling
6.8K
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,...
6.8K
Protein Kinases and Phosphatases
15.4K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.4K
Feedback Regulation of Calcium Concentration
4.1K
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...
4.1K
Roles of Electrolytes: Calcium and Phosphate
1.4K
Calcium and phosphate are essential electrolytes in the human body, with calcium being the most abundant mineral. Around 99% of the body's calcium is stored in the skeleton and teeth, forming a crystal lattice of mineral salts in combination with phosphates. Calcium plays crucial roles in various bodily functions such as blood clotting, neurotransmitter release, muscle tone maintenance, and nervous and muscle tissue excitability.
The calcium concentration in blood plasma is primarily...
The calcium concentration in blood plasma is primarily...
1.4K


