拉力不同影响重新折叠路径由于SARS-CoV-1和SARS-CoV-2受体结合域的纠错误折叠状态
Pham Dang Lan1,2, Edward P O'Brien3,4,5, Mai Suan Li6
1Institute for Computational Sciences and Technology, Ho Chi Minh City 71506, Vietnam.
Biomolecules
|October 26, 2024
概括
单分子力光谱显示,SARS-CoV-2受体结合域 (RBD) 的重新折叠在力下减缓,与贝尔理论一致. 然而,SARS-CoV-1 RBD重新折叠不受强力影响,因为错误折叠最小化.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 单分子力光谱 (SMFS) 探测了受力下的蛋白质动态.
- 贝尔理论预测蛋白质折叠时间的指数增长与施加的力.
- 冠状病毒的受体结合域 (RBD) 对于病毒进入至关重要.
研究的目的:
- 使用分子动力学模拟来研究SARS-CoV-1和SARS-CoV-2受体结合域 (RBD) 的重新折叠途径.
- 在贝尔理论的背景下,比较SARS-CoV-1 RBD和SARS-CoV-2 RBD对应用力的反应.
- 探索强力诱导的重新折叠行为的差异背后的分子机制.
主要方法:
- 使用粗粒度的分子动力学模拟.
- 模拟比较了展开的SARS-CoV-1 RBD和SARS-CoV-2 RBD的重新折叠路径,有或没有施加力 (5 pN).
- 对折叠形状的纠变化进行了分析.
主要成果:
- 一个5 pN的力量显著减少了SARS-CoV-2 RBD的重新折叠轨迹,与贝尔理论一致.
- 在5pN力下,SARS-CoV-1 RBD重新折叠时间没有显著变化.
- 外力最小化了SARS-CoV-1 RBD的错误折叠到动力捕获状态,促进了高效的折叠.
结论:
- 蛋白质重新折叠中的非钟声行为可能源于将错误折叠到动力捕获状态的最小化.
- 在SARS-CoV-1 RBD中错误折叠的状态包含在原生状态中不存在的非原生纠.
- 这项研究提出了一种潜在的实验方法,用于检测难以捉摸的,理论上预测的错误折叠状态.
相关概念视频
Amyloid Fibrils
9.3K
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,...
9.3K
Protein Folding Quality Check in the RER
3.7K
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...
3.7K
Molecular Chaperones and Protein Folding
17.8K
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...
17.8K
The Unfolded Protein Response
4.4K
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...
4.4K
Protein Folding
117.5K
Overview
117.5K
Mechanisms of Membrane-bending
2.6K
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
2.6K


