美国国立卫生研究院的Hoi Sung Chung研究组取得最新进展。他们发现无序的蛋白质在折叠并结合到伴侣时会遵循不同的过渡路径。相关论文于2020年6月12日发表于国际学术期刊《科学》杂志上。

他们使用快速的三色单分子Förster共振能量转移光谱来获得无序蛋白的结合过渡路径的分布。 大约一半的过渡遵循一条涉及强非天然静电相互作用的路径，从而导致300到800微秒的过渡时间。剩下的一半遵循多种多样的路径，这些路径的特征是弱的静电相互作用和短于十倍的过渡路径时间。链的柔韧性和非天然相互作用使多种结合途径成为可能，从而使无序蛋白的结合速度比折叠蛋白快。

研究人员表示，大分子构象变化（例如蛋白质折叠）的过渡路径预计为异质的。但是，对过渡路径的多样性进行实验表征非常具有挑战性，因为在单个过渡过程中需要测量多个距离。

附：英文原文

Title: Disordered proteins follow diverse transition paths as they fold and bind to a partner

Author: Jae-Yeol Kim, Hoi Sung Chung

Issue&Volume: 2020/06/12

Abstract: Transition paths of macromolecular conformational changes such as protein folding are predicted to be heterogeneous. However, experimental characterization of the diversity of transition paths is extremely challenging because it requires measuring more than one distance during individual transitions. In this work, we used fast three-color single-molecule Frster resonance energy transfer spectroscopy to obtain the distribution of binding transition paths of a disordered protein. About half of the transitions follow a path involving strong non-native electrostatic interactions, resulting in a transition time of 300 to 800 microseconds. The remaining half follow more diverse paths characterized by weaker electrostatic interactions and more than 10 times shorter transition path times. The chain flexibility and non-native interactions make diverse binding pathways possible, allowing disordered proteins to bind faster than folded proteins.

DOI: 10.1126/science.aba3854

Source: https://science.sciencemag.org/content/368/6496/1253