Rapid Filament Supramolecular Chirality Reversal of HET-s (218鈥?89) Prion Fibrils Driven by pH Elevation

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• 作者：Maruda Shanmugasundaram ; Dmitry Kurouski ; William Wan ; Gerald Stubbs ; Rina K. Dukor ; Laurence A. Nafie ; Igor K. Lednev
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：July 9, 2015
• 年：2015
• 卷：119
• 期：27
• 页码：8521-8525
• 全文大小：247K
• ISSN：1520-5207

文摘

Amyloid fibril polymorphism is not well understood despite its potential importance for biological activity and associated toxicity. Controlling the polymorphism of mature fibrils including their morphology and supramolecular chirality by postfibrillation changes in the local environment is the subject of this study. Specifically, the effect of pH on the stability and dynamics of HET-s (218鈥?89) prion fibrils has been determined through the use of vibrational circular dichroism (VCD), deep UV resonance Raman, and fluorescence spectroscopies. It was found that a change in solution pH causes deprotonation of Asp and Glu amino acid residues on the surface of HET-s (218鈥?89) prion fibrils and triggers rapid transformation of one supramolecular chiral polymorph into another. This process involves changes in higher order arrangements like lateral filament and fibril association and their supramolecular chirality, while the fibril cross-尾 core remains intact. This work suggests a hypothetical mechanism for HET-s (218鈥?89) prion fibril refolding and proposes that the interconversion between fibril polymorphs driven by the solution environment change is a general property of amyloid fibrils.