Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin
Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin
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DOI：
10.1073/pnas.0901213106
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发表时间：
2009-06-30
影响因子：
11.1
通讯作者：
Fernandez, Julio M.
中科院分区：
文献类型：
--
作者：
Garcia-Manyes, Sergi;Dougan, Lorna;Fernandez, Julio M.
蛋白质折叠的统计理论早就预测了通过不同的结构集合减少巨大构象空间的合理机制。然而，这些预测仍然没有通过批量技术进行测试，因为折叠分子的构象多样性在实验上是不可接近的。由于单分子力钳光谱学的最新进展，我们现在能够探测的结构和动力学的小蛋白泛素通过测量其长度和机械稳定性在每个阶段的折叠。在这里，我们发现，在疏水性崩溃，蛋白质迅速选择一个子集的最小能量结构，是机械薄弱和必要的前体的天然折叠。从这个大大减少合奏，通过势垒有限的过渡获得的原生状态。我们的研究结果支持统计力学模型在描述生物时标上的小蛋白质折叠的有效性。
Statistical theories of protein folding have long predicted plausible mechanisms for reducing the vast conformational space through distinct ensembles of structures. However, these predictions have remained untested by bulk techniques, because the conformational diversity of folding molecules has been experimentally unapproachable. Owing to recent advances in single molecule force-clamp spectroscopy, we are now able to probe the structure and dynamics of the small protein ubiquitin by measuring its length and mechanical stability during each stage of folding. Here, we discover that upon hydrophobic collapse, the protein rapidly selects a subset of minimum energy structures that are mechanically weak and essential precursors of the native fold. From this much reduced ensemble, the native state is acquired through a barrier-limited transition. Our results support the validity of statistical mechanics models in describing the folding of a small protein on biological timescales.