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一种关于大分子拥挤和表面吸附对线性蛋白质原纤维形成的联合效应的平衡模型。

An equilibrium model for the combined effect of macromolecular crowding and surface adsorption on the formation of linear protein fibrils.

作者信息

Hoppe Travis, Minton Allen P

机构信息

Section on Physical Biochemistry, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Section on Physical Biochemistry, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

出版信息

Biophys J. 2015 Feb 17;108(4):957-966. doi: 10.1016/j.bpj.2014.12.033.

Abstract

The formation of linear protein fibrils has previously been shown to be enhanced by volume exclusion or crowding in the presence of a high concentration of chemically inert protein or polymer, and by adsorption to membrane surfaces. An equilibrium mesoscopic model for the combined effect of both crowding and adsorption upon the fibrillation of a dilute tracer protein is presented. The model exhibits behavior that differs qualitatively from that observed in the presence of crowding or adsorption alone. The model predicts that in a crowded solution, at critical values of the volume fraction of crowder or intrinsic energy of the tracer-wall interaction, the tracer protein will undergo an extremely cooperative transition-approaching a step function-from existence as a slightly self-associated species in solution to existence as a highly self-associated and completely adsorbed species. Criteria for a valid experimental test of these predictions are presented.

摘要

先前的研究表明,在高浓度化学惰性蛋白质或聚合物存在的情况下,体积排除或拥挤效应以及吸附到膜表面会增强线性蛋白质原纤维的形成。本文提出了一个平衡介观模型,用于描述拥挤效应和吸附作用对稀示踪蛋白纤维化的综合影响。该模型表现出的行为与单独存在拥挤效应或吸附作用时观察到的行为在性质上有所不同。该模型预测,在拥挤溶液中,当拥挤剂的体积分数或示踪剂 - 壁相互作用的内在能量达到临界值时,示踪蛋白将经历一个极其协同的转变——接近阶跃函数——从溶液中轻微自缔合的物种转变为高度自缔合并完全吸附的物种。本文还给出了对这些预测进行有效实验验证的标准。

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