在真核生物中控制的双模块机制
Henning Tidow1, Lisbeth R Poulsen, Antonina Andreeva
1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Aarhus University, Gustav Wieds Vej 10c, DK-8000 Aarhus C, Denmark.
Nature
|October 23, 2012
概括
细胞通过使用血膜Ca2+-ATPases (PMCA) 严格控制 (Ca2+) 水平. 这项研究揭示了一种两步激活机制,其中两个卡尔莫杜林分子调节PMCA活性,确保精确的平衡.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 离子 (Ca2+) 是细胞信号传输中的关键次要信使.
- 保持的细胞内和细胞外Ca2+梯度对于细胞功能至关重要.
- 血膜Ca2+-ATPases (PMCA) 是细胞内Ca2+的关键调节者.
研究的目的:
- 阐明卡尔莫杜林介导的PMCA激活的结构基础.
- 了解PMCA调节如何适应不同的细胞内Ca2+度.
- 提供对PMCA两步激活过程的机制性见解.
主要方法:
- 一个PMCA调节域/calmodulin复合体的高分辨率晶体结构的确定.
- 在体内表征.
- 生物化学,生物物理和生物信息学分析.
主要成果:
- 晶体结构显示了calmodulin与PMCA调节域结合的2:1固态度.
- 在长螺旋上发现了含量的calmodulin的两个不同的结合点.
- 为卡尔莫杜林介导的PMCA调控建立了一个全面的模型.
结论:
- 卡尔莫杜林介导的PMCA调节包括一个两步激活机制.
- 鉴定到的结合部位和固体测量解释了细胞内Ca2+的严格和响应性控制.
- 这种机制使得真核细胞能够保持稳定的基底Ca2+水平,并对Ca2+过渡物做出反应.
相关概念视频
Feedback Regulation of Calcium Concentration
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...
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The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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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.
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Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
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