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静电控制着蛋白质聚集过程中淀粉样超结构的形成。

Electrostatics controls the formation of amyloid superstructures in protein aggregation.

机构信息

Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.

Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom and Theory of Condensed Matter, Department of Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.

出版信息

Phys Rev Lett. 2013 Sep 6;111(10):108105. doi: 10.1103/PhysRevLett.111.108105. Epub 2013 Sep 5.

DOI:10.1103/PhysRevLett.111.108105
PMID:25166715
Abstract

The possibility for proteins to aggregate in different superstructures, i.e. large-scale polymorphism, has been widely observed, but an understanding of the physicochemical mechanisms behind it is still out of reach. Here we present a theoretical model for the description of a generic aggregate formed from an ensemble of charged proteins. The model predicts the formation of multifractal structures with the geometry of the growth determined by the electrostatic interactions between single proteins. The model predictions are successfully verified in comparison with experimental curves for aggregate growth allowing us to reveal the mechanism of formation of such complex structures. The model is general and is able to predict aggregate morphologies occurring both in vivo and in vitro. Our findings provide a framework where the physical interactions between single proteins, the aggregate morphology, and the growth kinetics are connected into a single model in agreement with the experimental data.

摘要

蛋白质在不同超结构中聚集的可能性,即大规模多态性,已被广泛观察到,但对其背后的物理化学机制的理解仍遥不可及。在这里,我们提出了一个理论模型,用于描述由带电蛋白质组成的集合形成的通用聚集体。该模型预测了具有由单蛋白质之间的静电相互作用确定的生长几何形状的多分形结构的形成。通过与聚集体生长的实验曲线进行比较,成功地验证了模型预测,从而揭示了形成这种复杂结构的机制。该模型是通用的,能够预测体内和体外发生的聚集体形态。我们的发现提供了一个框架,其中单蛋白质之间的物理相互作用、聚集体形态和生长动力学连接成一个与实验数据一致的单一模型。

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