蛋白的八重复域在pH7.4时与三种不同的协调模式结合Cu
Madhuri Chattopadhyay1, Eric D Walter, Dustin J Newell
1Department of Chemistry & Biochemistry, University of California, Santa Cruz, California 95064, USA.
蛋白 (PrP) 通过其八重复域将铜离子 (Cu2+) 结合起来. 这项研究揭示了pH7.4的三种不同的铜协调模式,澄清了PrPP.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生物有机化学 生物有机化学
背景情况:
- 蛋白的N端八重复组域与Cu2+离子结合.
- 基本的重复序列是PHGGGWGQ.
- 之前的研究表明,完全的铜占用涉及每个HGGGW段绑定一个Cu2+.
研究的目的:
- 为了研究低铜占用处的蛋白八重复域中的铜协调模式.
- 探索希斯蒂丁残留物在替代协调中的潜在参与.
- 描述八重重复域中依赖铜的结构变化.
主要方法:
- 使用X波段电子偏磁共振 (EPR),S波段 EPR和电子自旋回声封面调制 (ESEEM).
- 采用了一系列修饰的图书馆,以促进特定的协调相互作用.
- 在pH 7.4.4下分析铜协调模式.
主要成果:
- 在pH值7.4.4时识别并充分描述了三种不同的铜协调模式.
- 证实了在低铜固体测量时的多重histidine协调.
- 在完全占用时检测到铜-铜相互作用,表明域崩和合作性铜吸收.
结论:
- 提供了PrP八重复域在pH7.4的7.4重复域中主要铜协调模式的第一个全面表征.
- 阐明了不同度的铜结合的结构基础.
- 突出了低铜环境中胺协调的作用和高铜环境中域崩的作用.
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