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多个本土状态揭示了RNA折叠景观的持续粗性

Sergey V Solomatin¹, Max Greenfeld, Steven Chu

¹Department of Biochemistry, Stanford University, Stanford, California 94305, USA.

|February 5, 2010

概括

像RNA这样的生物巨分子可以折叠成多个不同的原生状态,挑战单一能量最小的传统观点. 在RNA折叠景观中的这种粗性影响了活性构造.

科学领域:

生物化学生物化学
分子生物学分子生物学
结构生物学结构生物学

背景情况:

热力学假设认为,宏分子的序列决定了独特的本地结构作为全球能量最小值.
对于大型宏分子而言,复杂的折叠景观引发了关于超出单个全球最小值的多个稳定,活跃构造的存在的问题.
虽然一些蛋白质遵循双态折叠模型,但证据表明,具有相互转换的活性状态的更复杂的景观.

研究的目的:

通过单分子实验来研究RNA酶的折叠景观拓.
为了确定RNA酶是否折叠成多个不同的原生状态.
评估这些原生状态之间的相互转换的时间尺度.

主要方法:

利用单分子实验来探测RNA折叠动态.
分析了RNA酶的构造格局.

主要成果:

证明RNA酶折叠成多个不同的原生状态.
表明这些原生状态之间的相互转换发生在比催化作用更长的时间尺度上.
提供了RNA折叠景观延伸到原生构造空间的粗性证据.

结论:

RNA折叠景观是复杂和崎的,延伸到原生状态的构造空间.
存在多个,缓慢相互转换的原生状态的存在挑战了宏分子折叠的简化模型.
这一发现对理解RNA功能和进化有重要意义.

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