人类PKD1-PKD2复合物的结构
Qiang Su1, Feizhuo Hu1, Xiaofei Ge1
1Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Science (New York, N.Y.)
|August 11, 2018
概括
自体主导多囊性病 (ADPKD) 与PKD1和PKD2基因突变有关. 研究人员揭示了PKD1-PKD2复杂结构,揭示了非正规的TRP通道结构,这可能解释ADPKD疾病机制.
科学领域:
- 结构生物学
- 分子生物学
- 遗传学
背景情况:
- 自体主导性多囊性病 (ADPKD) 是一种普遍存在的单一性疾病.
- 大多数ADPKD病例的原因是 *PKD1* 和 *PKD2* 基因的突变.
- 了解PKD1-PKD2复合体的结构对于阐明ADPKD病原性至关重要.
研究的目的:
- 确定人体PKD1-PKD2复合物的冷电子显微镜结构.
- 描述PKD1-PKD2复合体的结构,并确定关键的功能领域.
- 为了解PKD蛋白的功能和疾病机制提供结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定截断的人类PKD1- PKD2复合物的结构.
- 该复合物以PKD1与PKD2的比例为1:3组装.
- 高分辨率的结构分析在3.6安格斯特罗姆进行.
主要成果:
- 该结构显示了由PKD1和PKD2相互作用形成的非正规的短暂受体潜力 (TRP) 通道结构.
- PKD1表现出电压关离子通道 (VGIC) 折叠,具有独特的破碎S6螺旋.
- 该结构在PKD1中发现了五个跨膜螺旋域和细胞质PLAT域,以及潜在的阴离子阻断残留物.
结论:
- 该PKD1-PKD2复合体的确定的结构为该关键离子通道的分子结构提供了前所未有的见解.
- 这些发现为了解PKD1和PKD2突变如何导致ADPKD提供了框架.
- 这些结构信息对于未来对ADPKD功能机制和治疗策略的研究至关重要.
相关概念视频
01:32Assembly of Complex Microtubule Structures
2.5K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
2.5K
01:18Structural Organization of the Human Body: An Overview
29.5K
It is convenient to consider the body's structures in terms of fundamental levels of organization that increase in complexity: subatomic particles, atoms, molecules, organelles, cells, tissues, organs, organ systems, and organisms.
To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms, and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of...
To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms, and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of...
29.5K
02:40Chromosome Structure
26.6K
A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
26.6K
02:34Structural Isomerism
21.7K
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...
21.7K
02:41Protein Complex Assembly
16.8K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.8K
01:57Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K