一种广泛的蛋白质错误折叠机制是基于基因本质性的陪伴者差异性地拯救的
Ian Sitarik1, Quyen Vu1, Justin Petucci2
1Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, United States.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
与非共价拉索纠 (NCLE) 相关的蛋白质错折是普遍存在的. 陪伴者往往无法纠正非必需蛋白质中的这种错误折叠,与必需蛋白质不同.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 蛋白质错误折叠与疾病和细胞功能障碍有关.
- 非共价拉索纠 (NCLE) 已被提出作为一种结构动机,涉及蛋白质错折.
- 之前关于NCLE误折叠的研究仅限于少数蛋白质.
研究的目的:
- 调查与非共价拉索纠 (NCLE) 相关的蛋白质错误折叠的流行和机制,在全蛋白质组范围内.
- 确定DnaK和GroEL等分子伴侣在重新折叠NCLE错误折叠蛋白质中的作用.
- 探索特定于序列的适应,可以促进从NCLE错误折叠中以护送为媒介的救援.
主要方法:
- 整合了E.E. 的整合. 大肠杆菌的全蛋白质组有限的蛋白质分解质谱数据与原生蛋白质结构数据集.
- 统计分析以将NCLE的存在与错误折叠的可能性和陪伴者救援效率相关联.
- 分子动力学模拟以阐明NCLE错折和循环关闭的机制.
主要成果:
- 具有本地NCLE的蛋白质错折的可能性是NCLE区域错折的两倍,错折集中在NCLE区域.
- 与非必需蛋白相比,必需蛋白更有可能通过DnaK和GroEL的陪伴者从NCLE错误折叠中得到拯救.
- 分子模拟揭示了NCLE循环过早关闭的机制,导致持续的错误折叠状态.
结论:
- 非共价拉索纠 (NCLE) 错误折叠是一种普遍的现象,影响了数百种蛋白质.
- 护航系统对NCLE错折表现出差异性的救援活动,特别是区分基本和非基本蛋白质.
- 蛋白质序列可能会进化,以允许伴侣介导的NCLE错折的纠正,这表明针对这种类型的蛋白质功能障碍的适应性策略.
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