PAP ((248-286) 在粉样纤维素形成的滞后阶段的形状变化
Aleksandra M Kusova1,2, Aydar R Yulmetov1, Dmitriy S Blokhin1
1Kazan Federal University, Kremlevskaya Str., 18, 420008 Kazan, Russia.
Biochemistry
|May 29, 2023
概括
这项研究揭示了前列腺酸酸酶 (PAP) 单体在粉样纤维素形成过程中如何改变形状. 这些结构变化是由与现有纤维的相互作用驱动的,对于二次核形成过程至关重要.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 前列腺酸酶 (PAP) 是一种人类精液等离子体蛋白.
- PAP的C端区域,特别是PAP248-286,形成被称为精液衍生的病毒感染增强剂 (SEVI) 的粉样纤维.
- 塞维在精液中丰富,在病毒感染增强中发挥作用.
研究的目的:
- 为了研究PAP的初始阶段 ((248-286) 粉样纤维的形成.
- 在二次核化过程中描述PAP单体的结构变化 248-286).
- 了解纤维素-单体相互作用背后的分子机制.
主要方法:
- 脉冲场梯度 (PFG) NMR光谱学用于研究溶液中的单体行为.
- 高分辨率的NMR光谱检测结构变化.
- 分子动力学 (MD) 模拟以建模形状.
主要成果:
- 二次核化涉及PAP ((248-286) 单体和成熟纤维之间的相互作用.
- 在与纤维细胞种子相互作用时,PFG NMR揭示了单体紧缩.
- 核磁共振和核磁共振模拟显示PAP ((248-286) 通过脊柱曲在H270和T275.5周围折叠.
- 折叠的构造在单体-粉样相互作用后,在能量方面是有利的和稳定的.
- 结构变化涉及疏水区域的暴露,促进单体-粉样相互作用.
结论:
- 这项研究阐明了二次核化过程中PAP ((248-286)) 单体的结构转化.
- 纤维素-单体相互作用诱导一个稳定的,折叠的形状在PAP ((248-286).
- 疏水性相互作用是观察到的单质粉样蛋白结合机制的关键.
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