伪-Synuclein鈥檚 Adsorption, Conformation, and Orientation on Cationic Gold Nanoparticle Surfaces Seeds Global Conformation Change

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• 作者：Jie An Yang ; Wayne Lin ; Wendy S. Woods ; Julia M. George ; Catherine J. Murphy
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：April 3, 2014
• 年：2014
• 卷：118
• 期：13
• 页码：3559-3571
• 全文大小：656K
• 年卷期：v.118,no.13(April 3, 2014)
• ISSN：1520-5207

文摘

伪-Synuclein (伪-syn), an aggregation-prone amyloid protein, has been suggested as a potential cause of Parkinson鈥檚 disease. When misfolded, 伪-syn aggregates as Lewy bodies in the brain, the loss of which can disrupt protein homeostasis. To investigate the potential of nanoparticle-mediated therapy for amyloid diseases, 伪-syn adsorption onto positively charged poly(allylamine hydrochloride) coated gold nanoparticles (PAH Au NPs) was studied. 伪-Syn adsorbs in multilayers onto PAH Au NPs, which with increasing 伪-syn/PAH Au NP ratios (>2000 伪-syn/PAH Au NP) results in the flocculation and sedimentation of 伪-syn coated PAH Au NPs. The orientation and conformation of 伪-syn on PAH Au NPs were studied using trypsin digestion and circular dichroism, which showed that 伪-syn adopts a random orientation on PAH Au NPs, with an increase in 尾-sheet and a decrease in 伪-helix structures. A consistent global change in 伪-syn鈥檚 conformation was also observed regardless of PAH Au NP concentration, suggesting bound 伪-syn initiates conformational changes to free 伪-syn.