由疾病突变加速的ALS蛋白质FUS的液态到固态过渡
Avinash Patel1, Hyun O Lee1, Louise Jawerth2
1Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Cell
|August 29, 2015
概括
像FUS这样的无序区域的蛋白质可以形成对功能至关重要的液体区,但容易聚合. 这些区间的异常阶段过渡与神经退行性疾病 (如肌缩侧面硬化症 (ALS)) 有关.
科学领域:
- 生物化学
- 分子生物学
- 神经科学
背景情况:
- 许多蛋白质本质上具有易于聚合的区域, 导致与年龄相关的疾病.
- 涉及肌缩侧面硬化症 (ALS) 的FUS蛋白含有这种失序的域,并表现出类似的特性.
研究的目的:
- 研究FUS蛋白的生理作用.
- 了解FUS液体区间向聚合状态的过渡及其与ALS病变的联系.
主要方法:
- 在DNA损伤部位和细胞质应激期间观察FUS局部化的细胞研究.
- 在体外溶解液体FUS区.
- 实验室老化实验以监测随着时间的推移,液体转化为聚合物.
主要成果:
- 在特定条件下 (DNA损伤,压力) 和体外,FUS蛋白在细胞中形成动态液体区.
- 在试验室中老化表明液体FUS滴转化为聚合状态.
- 患者引发的突变加速了这种液体转化.
结论:
- 动态的液体状区块对于FUS蛋白的生理功能至关重要.
- 这些区块在功能和聚合风险之间进行了权衡.
- 在FUS液体区的异常阶段过渡被认为是ALS和其他与年龄有关的疾病的关键机制.
相关概念视频
Amyloid Fibrils
13.0K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
13.0K
Amyloid Fibrils
7.0K
7.0K
Phase Transitions
23.9K
Whether solid, liquid, or gas, a substance's state depends on the order and arrangement of its particles (atoms, molecules, or ions). Particles in the solid pack closely together, generally in a pattern. The particles vibrate about their fixed positions but do not move or squeeze past their neighbors. In liquids, although the particles are closely spaced, they are randomly arranged. The position of the particles are not fixed—that is, they are free to move past their neighbors to...
23.9K
Cooperative Allosteric Transitions
2.8K
2.8K
Cooperative Allosteric Transitions
9.4K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
9.4K
Translation
161.3K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
161.3K


