阴离子-联输送体NKCC1的结构和机制
Thomas A Chew1,2, Benjamin J Orlando3, Jinru Zhang1
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|August 2, 2019
概括
研究人员确定了Na-K-Cl共传输体 (NKCC1) 的冷电子显微镜结构. 这揭示了载体的结构,离子通路和结合点,有助于理解其功能和相关疾病.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生理学分子生理学
背景情况:
- 阴离子-合运输体 (CCC) 是重要的膜蛋白调节离子运输.
- 它们在细胞体积,上皮离子运输和细胞内化物平衡中起着关键作用.
- 对于许多被广泛处方的药物来说,CCC是关键的目标.
研究的目的:
- 为了确定来自丹尼奥 rerio 的 Na-K-Cl 共传输体 1 (NKCC1) 的冷电子显微镜结构.
- 阐明CCC蛋白家族的结构结构.
- 了解离子运输,选择性和合的机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于高分辨率的结构确定.
- 功能性特征分析用于评估运输活动.
- 计算研究分析离子通路和结合点.
主要成果:
- 该研究介绍了NKCC1的冷EM结构,定义了其整体结构.
- 确定了关键的离子结合点和离子转位途径.
- 确定了涉及运输活动的关键残留物.
结论:
- NKCC1结构为理解CCC家族架构和功能提供了一个框架.
- 获得了对离子选择性,合和转位机制的洞察力.
- 这些结构和功能数据将有助于解释影响CCC的疾病相关突变.
相关概念视频
Cationic Chain-Growth Polymerization: Mechanism
2.8K
The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the...
2.8K
Aromatic Hydrocarbon Cations: Structural Overview
3.6K
Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group...
Removing one hydrogen from the intervening CH2 group...
3.6K
Ionic Crystal Structures
16.9K
Ionic crystals consist of two or more different kinds of ions that usually have different sizes. The packing of these ions into a crystal structure is more complex than the packing of metal atoms that are the same size.
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
16.9K
Roles of Electrolytes: Chloride and Bicarbonate
936
Chloride ions contribute to the osmotic pressure gradient distinguishing the intracellular fluid (ICF) from the extracellular fluid (ECF). They counterbalance positively charged ions in the ECF and ensure its electrochemical stability. The renal system's process of chloride absorption and release generally mirrors that of sodium ions.
Conditions such as hypochloremia can arise from insufficient chloride reabsorption by the kidneys, often compounded by extended bouts of diarrhea, vomiting,...
Conditions such as hypochloremia can arise from insufficient chloride reabsorption by the kidneys, often compounded by extended bouts of diarrhea, vomiting,...
936
Carboxylic Acids to Acid Chlorides
8.7K
Carboxylic acids react with SOCl2 or PCl5 to form acid chlorides. Amongst the carboxylic acid derivatives, acid chlorides are the most reactive and synthetically important derivatives. They are useful reagents for Friedel–Crafts acylation of some aromatic compounds.
8.7K
Structural Isomerism
21.5K
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can...
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can...
21.5K


