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蛋白质折叠、聚集和淀粉样蛋白组装过程中的水合作用、空洞与体积

Hydration, cavities and volume in protein folding, aggregation and amyloid assembly.

作者信息

Silva Jerson L, Foguel Debora

机构信息

Instituto de Bioquímica Médica and Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Phys Biol. 2009 Feb 10;6(1):015002. doi: 10.1088/1478-3975/6/1/015002.

DOI:10.1088/1478-3975/6/1/015002
PMID:19208935
Abstract

Differential hydration dictates various biological processes, including protein folding, ligand binding, macromolecular assembly, enzyme kinetics and signal transduction. If water is partially or totally removed (experimentally or in silico), the outcome of these processes can be significantly affected. The aggregation of proteins into amyloids or other aggregate forms also results in profound changes in hydration. High hydrostatic pressure is a unique tool to study hydration, as increases in water binding usually lead to decreases in volume. Pressure changes can favor the formation or disassembly of amyloids depending on the volume changes associated with protein folding and misfolding/aggregation. The packing and formation of cavities will also contribute to changes in volume, and therefore, to sensitivity to pressure. Therefore, the formation of water-excluding cavities is predicted to be an important event in folding and aggregation landscapes.

摘要

差异水合作用决定了各种生物过程,包括蛋白质折叠、配体结合、大分子组装、酶动力学和信号转导。如果水被部分或完全去除(通过实验或计算机模拟),这些过程的结果可能会受到显著影响。蛋白质聚集成淀粉样蛋白或其他聚集形式也会导致水合作用的深刻变化。高静水压力是研究水合作用的独特工具,因为水结合的增加通常会导致体积减小。压力变化根据与蛋白质折叠和错误折叠/聚集相关的体积变化,可能有利于淀粉样蛋白的形成或分解。空穴的堆积和形成也将导致体积变化,因此导致对压力的敏感性。因此,预计排除水的空穴的形成是折叠和聚集过程中的一个重要事件。

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