由内在无序的部分产生的力调整蛋白质功能
Nicholas D Keul1, Krishnadev Oruganty2, Elizabeth T Schaper Bergman3
1Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
Nature
|November 14, 2018
概括
本质上无序的片可以通过转移形态组合来增强蛋白质功能. 这种由无序区域的长度驱动的热效应优化了UDP-α-D-葡萄糖-6-脱酶 (UGDH) 的抑制剂结合.
科学领域:
- 生物化学
- 结构生物学
- 进化生物学
背景情况:
- 蛋白质结构是动态的,探索各种对功能至关重要的结构.
- 蛋白质进化和功能中的内在无序区域的作用尚不清楚.
- 人类蛋白质组的很大一部分含有未知功能的内在无序部分.
研究的目的:
- 调查内在无序的片如何影响蛋白质构成和功能.
- 确定本质上失序的碳酸终端影响蛋白质 - 连接体相互作用的机制.
- 在蛋白质适应过程中探索内在无序部分的进化含义.
主要方法:
- 研究了人类的UDP-α-D-葡萄糖-6-脱酶 (UGDH) 蛋白质.
- 研究了内在无序的碳酸终端尾 (ID-尾) 对UGDH的形状组合的影响.
- 分析了ID尾部长度与异质抑制剂的亲和关系.
主要成果:
- ID尾部将UGDH形态组合转移到一种对全抑制剂的更高亲和度的状态.
- 观察到的亲和度增强取决于内在无序段的长度,而不是其序列或组成.
- 这种效应与非结构化产生的力一致.
结论:
- 本质上是无序的尾巴作为一个"直器",通过调节蛋白质动态和结构来促进抑制剂的结合.
- 这种机制提供了易于获得的适应性,表明进化可能会选择无序的部分来调整蛋白质能量格局.
- 这些发现为蛋白质组内在疾病的流行提供了潜在的解释.
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