脂质结合蛋白的全球地图及其在细胞中的结合性
Micah J Niphakis1, Kenneth M Lum1, Armand B Cognetta1
1The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|June 20, 2015
概括
研究人员开发了新的化学探针来绘制细胞中脂质-蛋白质相互作用的地图. 这揭示了脂质通路内的新药标,扩大了我们对细胞脂质调节和疾病机制的理解.
科学领域:
- 生物化学 生物化学
- 化学生物学 化学生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 脂质对细胞功能至关重要,蛋白质相互作用调解它们在健康和疾病中的作用.
- 了解这些脂质-蛋白质相互作用是解读复杂生物通路的关键.
研究的目的:
- 创建和利用基于脂质的化学蛋白质探针,在全球范围内绘制哺乳动物细胞中的蛋白质相互作用.
- 为了确定新的药物点,并在脂质相互作用蛋白质组内表征药物作用.
主要方法:
- 开发基于脂质的化学蛋白质探针.
- 哺乳动物细胞中蛋白质相互作用的全球映射.
- 在脂质相互作用蛋白质组内确定药物标配置文件.
- 对核丁-1 (NUCB1) 的选择性配体的合成和测试.
主要成果:
- 识别了数百种与不同功能类别的脂质相互作用的蛋白质.
- 证明脂蛋白相互作用经常发生在药物作用部位.
- 揭示了脂质相互作用蛋白质组包含了传统类别之外的众多可结合的目标.
- 一个选择性的NUCB1连接体被证明可以调节内分泌类大麻素代谢.
结论:
- 化学蛋白质组平台提供了一种全面的方法来发现和药理学描述参与细胞脂质通路的蛋白质.
- 这项工作通过突出与脂质相互作用的蛋白质来扩大可药物点的景观.
- 这些发现为治疗脂质相关疾病的治疗干预提供了新的途径.
相关概念视频
Lipids as Anchors
8.0K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
8.0K
Ligand Binding Sites
15.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.8K
Ligand Binding Sites
9.1K
9.1K
Membrane Lipids
35.7K
Lipids are an essential component of all biological membranes. The average lipid content in mammalian membranes is 50%, though it can be as low as 20% in the inner mitochondrial membrane or as high as 80% in the myelin sheath present around the nerve cells.
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
35.7K
Membrane Fluidity
18.1K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
18.1K
Membrane Fluidity
179.6K
Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
179.6K


