相关实验视频
Updated: Sep 13, 2025

12:42
Microfluidic Mixers for Studying Protein Folding
Published on: April 10, 2012
15.2K
识别路径中的中间体揭示了蛋白质折叠和失折之间的动力竞争
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556.
概括
大型蛋白质折叠是复杂的. 研究人员确定了一种短暂的中间体 (PFS*),它指导从C端到N端的形素 (P.69T) 的折叠,克服了错误折叠的挑战.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质折叠的复杂性随着蛋白质的大小而增加.
- 较大的蛋白质面临着难以在复杂的能量场景中导航的挑战,原因是路径外的错误折叠.
- 之前对动素 (P.69T) 的研究显示,折叠速度缓慢,动力上被困的部分折叠状态 (PFS).
研究的目的:
- 为了描述P.69T.的难以捉摸的在路径上的折叠中间体.
- 了解中间体如何影响大蛋白质的折叠通路.
- 为了阐明P.69Tβ螺旋乘客域的折叠机制.
主要方法:
- 开发一种双跳"变质剂挑战"试验,利用缓慢展开的动力学.
- 使用开发的测定方法,对一种短暂的展开中间体 (PFS*) 进行表征.
- P.69T折叠中间体的结构和运动分析.
主要成果:
- 识别了一种短暂的展开中间体,PFS*,结构上类似于PFS,但展开速度更快.
- 证明PFS*在P.69T折叠中充当通路中的中间体.
- 支持P.69T的C到N终端折叠模型,以PFS*作为速度限制步骤.
结论:
- PFS*是P.69T折叠的关键路径中介物,位于折叠/错折的动力竞争点.
- P.69T的折叠从C端到N端过程性地发生,即使是在穿过细菌外膜的转位过程中.
- 在大型蛋白质折叠过程中,动力学在导航复杂的能量场景中发挥着至关重要的作用.
相关概念视频
Molecular Chaperones and Protein Folding
18.5K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.5K
Protein Folding
8.7K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.7K
Protein Folding Quality Check in the RER
3.8K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.8K
The Unfolded Protein Response
5.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.1K
Bacterial Protein Maturation
88
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
88
Export of Misfolded Proteins out of the ER
3.9K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.9K

