Macromolecular and Small Molecular Crowding Have Similar Effects on α-Synuclein Structure

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• 作者：Jia Bai ; Prof. Dr. Maili Liu ; Prof. Gary J. Pielak and Prof. Dr. Conggang Li
• 刊名：ChemPhysChem
• 出版年：2017
• 出版时间：January 4, 2017
• 年：2017
• 卷：18
• 期：1
• 页码：55-58
• 全文大小：863K
• ISSN：1439-7641

文摘

The intracellular milieu contains upwards of 400 g of macromolecules per liter. This crowding is thought to have a larger influence on intrinsically disordered proteins, whose chains are expanded, than on compact globular proteins. Classic theories of macromolecular crowding predict that increasing excluded volume effects will lead disordered proteins to compaction, and a great deal of data, from both simulation and experiments support this idea. We used nuclear magnetic resonance, circular dichroism, and fluorescence spectroscopies to characterize the structure and fibrillation of α-synuclein, an intrinsically disordered protein implicated in Parkinson's disease, using Ficoll70, its monomer sucrose and bovine serum albumin as crowding agents. Surprisingly, volume exclusion induced by high concentrations of macromolecules may not be the main reason for the compaction of α-synuclein. Our results indicate that all aspects crowding must be considered to understand protein conformation under crowded conditions.