相关实验视频

Updated: Jun 26, 2025

Purification of Hsp104, a Protein Disaggregase

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

Grp78感染性子的不稳定性是菌株特异性的,并受到多种因素的改变,包括辅助伴侣和pH值

Daniel Shoup¹, Suzette A Priola¹

¹Rocky Mountain Laboratories, Laboratory of Neurological Infections and Immunity, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

The Journal of biological chemistry

|May 8, 2024

概括

像Grp78这样的分子伴侣可以降低神经退行性疾病中的蛋白聚合物 (PrP^D). 这项研究表明,低pH值和其他伴侣物增强了Grp78.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
分子生物学分子生物学

背景情况:

致命的神经退行性子疾病源于积累错误折叠的子蛋白聚合物 (PrP^D).
像Grp78这样的分子陪伴物显示出减少PrP^D积累的潜力.
细胞环境和辅助者对Grp78对PrP^D的疗效的影响尚不清楚.

研究的目的:

为了研究两种适应小鼠疹菌株 (22L和87V) 的PrP^D的pH和蛋白酶介导的结构变化如何影响Grp78.8的处理.
确定共伴子 (Hsp90,DnaJC1,Stip1) 对Grp78修改PrP^D结构和促进分解的能力的影响.
探索PrP^D结构中的菌株特异性差异及其对伴侣活动的影响.

主要方法:

开发一种无细胞体外系统,以监测伴侣介导的结构变化和PrP^D的分解.
来自22L和87V菌株的PrP^D暴露在不同的pH条件和蛋白酶中.
评估GRP78单独和与HSP90,DnaJC1和Stip1.1结合的活性.

主要成果:

Grp78在低pH下显示了PrP^D的最大结构变化,尤其是在额外的伴侣存在时.
虽然被测试的陪伴者对PrP^D的完全分解是有限的,但蛋白酶预处理增强了22LPrP^D超过87VPrP^D的分解.
Hsp90诱导了87V PrP^D的结构变化,增加了它对N端蛋白解的敏感性.

结论:

伴奏子Grp78,DnaJC1,Stip1和Hsp90可能通过改变聚合物结构来促进蛋白聚合物 (PrP^D) 清除.
这些结构修改可以使PrP^D对蛋白酶敏感,这种方式取决于子菌株和pH值.
了解这些取决于菌株和pH值的相互作用对于开发对抗性疾病的治疗策略至关重要.

关键词:

Grp7878是什么意思陪伴者是一个陪伴者.分子陪伴者是一个分子陪伴者.普里昂是什么意思?普里昂是什么意思?病是普里翁病的一种疾病.蛋白质聚合蛋白质的聚合物蛋白质的稳定性蛋白质的稳定性

更多相关视频

Screening for Amyloid Aggregation by Semi-Denaturing Detergent-Agarose Gel Electrophoresis

Screening for Amyloid Aggregation by Semi-Denaturing Detergent-Agarose Gel Electrophoresis

Published on: July 16, 2008

Protein Misfolding Cyclic Amplification of Prions

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

相关概念视频

Molecular Chaperones and Protein Folding

Molecular Chaperones and Protein Folding

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...

Amyloid Fibrils

Amyloid Fibrils

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,...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

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...

Regulation of the Unfolded Protein Response

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...