囊性纤维化转膜导电调节器的原子结构
1The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Cell
|December 3, 2016
概括
研究人员可视化了斑马鱼囊性纤维化跨膜导电调节器 (CFTR) 的结构,揭示了其关机制和突变的影响. 这提供了关于囊性纤维化和潜在治疗点的见解.
科学领域:
- 生物化学
- 结构生物学
- 分子医学
背景情况:
- 囊性纤维化跨膜导电调节器 (CFTR) 是属于ATP结合盒 (ABC) 传输器超级家族的关键离子通道.
- CFTR功能障碍是囊性纤维化的一个根本原因, 这是一种影响多个器官的遗传疾病.
研究的目的:
- 为了确定斑马鱼的高分辨率CFTR在它的ATP贫乏状态.
- 阐明CFTR通道封闭和离子传导的结构基础.
- 了解囊性纤维化相关突变的分子机制.
主要方法:
- 使用电子冷显微镜 (cryo-EM) 解析斑马鱼的CFTR结构.
- 高分辨率结构分析以3.7 Ångström分辨率进行.
主要成果:
- 斑马鱼的CFTR结构显示出具有众多正电荷残留物的突出离子导电路.
- 在细胞外表面的单个门被确定为通道关闭的原因.
- 脱的调节域阻断了细胞内NBD接口,抑制了通道的开放.
结论:
- 确定的结构提供了CFTR封闭状态的详细视图,解释了突变如何导致折叠,导电或门缺陷.
- 这些结构信息为开发针对性治疗囊性纤维化提供了新的视角.
相关概念视频
Structure of Cadherins
5.1K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
5.1K
Multi-pass Transmembrane Proteins and β-barrels
6.8K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
6.8K
Protein Translocation Machinery on the ER Membrane
7.2K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
7.2K
Structure of Porins
4.1K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
4.1K
Insertion of Single-pass Transmembrane Proteins in the RER
18.6K
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
18.6K
The Supercomplexes in the Crista Membrane
3.1K
The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
3.1K


