根据Aspera ad Chaos:弗拉基米尔·乌弗斯基的奥德赛通过内在无序蛋白质的奇怪世界
Prakash Kulkarni1,2, Stefania Brocca3, A Keith Dunker4
1Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Biomolecules
|June 28, 2023
概括
人们认为蛋白质需要固定的3D结构才能发挥作用. 最近的研究挑战了这一点,表明蛋白质可以在没有单一,定义的形状的情况下发挥功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 从历史上看,蛋白质功能与独特的,稳定的三维 (3D) 结构密码在氨基酸序列内密码密切相关.
- 这种范式几十年来主导了分子生物学和生物化学,影响了研究方向和对蛋白质机制的解释.
研究的目的:
- 调查蛋白质功能的内在障碍的作用.
- 挑战长期以来的信念,即单一的,明确的3D结构是所有蛋白质活动的先决条件.
- 探索蛋白质结构功能关系的替代模型.
主要方法:
- 对内在无序区域的蛋白质数据库的分析.
- 蛋白质动态的计算建模.
- 在没有稳定的结构的情况下,对蛋白质功能的实验验证.
主要成果:
- 有证据表明,蛋白质组的很大一部分可能缺乏独特的,稳定的3D结构.
- 内在无序的蛋白质 (IDP) 和区域 (IDR) 具有不同的生物功能.
- 蛋白质的功能可以通过动态的形状组合而不是单一的静态结构来实现.
结论:
- 传统的结构-功能范式需要修订.
- 蛋白质的功能并不完全依赖于一个单一的,明确定义的3D结构.
- 固有无序蛋白质和区域的概念对于理解蛋白质能力的全谱至关重要.
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