分子觀點下的蛋白質摺疊、錯誤摺疊及其聚集

Understanding the Biophysical Mechanisms of Protein Folding, Misfolding, and Aggregation at Molecular Level

蔡惠旭(Gavin Hui-Hsu Tsai)

《化學》 63卷4期 (2005/12) Pp. 601-612

https://doi.org/10.6623/chem.2005048

摘要

本文從分子的觀點出發，首先討論蛋白質摺疊的基本物理化學原理，進而探討蛋白質錯誤摺疊及聚集狀態和蛋白質摺疊原理的關聯性。蛋白質異常聚集通常會形成類澱粉蛋白纖維而引發許多嚴重疾病，其中包括阿茲海默氏症、帕金森氏症及狂牛症。文中介紹最近在類澱粉蛋白纖維研究上的最新進展，包括類澱粉蛋白纖維分子結構之決定、分子動態法模擬類澱粉蛋白寡聚體形成之微觀機制及類澱粉蛋白纖維生成之巨觀機制。文末則介紹天然的β-sheet 蛋白質如何自我保護以防止它們彼此間的聚集。了解類澱粉蛋白纖維生成的生物物理機構，可提供藥物設計上重要資訊以預防蛋白質異常聚集及其相關疾病。

關鍵字

蛋白質摺疊 ； 蛋白質聚集 ； 類澱粉蛋白纖維 ； 神經退化性疾病 ； 漏斗模型 ； 分子自組 ； 分子動態法 ； 胺基酸堆疊

並列摘要

This article discussed the fundamental principles of protein folding and integrated the relationships of different states of proteins including protein folding, misfolding, aggregation, and amyloid formation. The aggregation of proteins usually results in the formation of amyloid fibrils and leads to several serve neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and mad cow diseases. The recent researches in amyloids including the determination of amyloid fibril structure, molecular dynamics simulations of the mechanisms of amyloid oligomer formation and the proposed mechanisms from kinetics point of view, are reviewed in details. Finally, the rules of how naturally-occurring -sheet proteins protect themselves from aggregation are discussed. Understanding the biophysical mechanisms of amyloid formation will provide important information for rational drug design and prevent their associated diseases.

並列關鍵字

Protein Folding ； Protein Aggregation ； Amyloid Fibril ； Neurodegenerative Diseases ； Funnel-Shape Model ； Molecular Self-Assembly ； Molecular Dynamics ； Amino Acid Stacking