Yang Jie An, Lin Wayne, Woods Wendy S, George Julia M, Murphy Catherine J
Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
J Phys Chem B. 2014 Apr 3;118(13):3559-71. doi: 10.1021/jp501114h. Epub 2014 Mar 24.
α-Synuclein (α-syn), an aggregation-prone amyloid protein, has been suggested as a potential cause of Parkinson's disease. When misfolded, α-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, α-syn adsorption onto positively charged poly(allylamine hydrochloride) coated gold nanoparticles (PAH Au NPs) was studied. α-Syn adsorbs in multilayers onto PAH Au NPs, which with increasing α-syn/PAH Au NP ratios (>2000 α-syn/PAH Au NP) results in the flocculation and sedimentation of α-syn coated PAH Au NPs. The orientation and conformation of α-syn on PAH Au NPs were studied using trypsin digestion and circular dichroism, which showed that α-syn adopts a random orientation on PAH Au NPs, with an increase in β-sheet and a decrease in α-helix structures. A consistent global change in α-syn's conformation was also observed regardless of PAH Au NP concentration, suggesting bound α-syn initiates conformational changes to free α-syn.
α-突触核蛋白（α-syn）是一种易于聚集的淀粉样蛋白，被认为是帕金森病的潜在病因。当发生错误折叠时，α-syn会在大脑中聚集成路易小体，路易小体的缺失会破坏蛋白质稳态。为了研究纳米颗粒介导的疗法对淀粉样疾病的治疗潜力，研究了α-syn在带正电荷的聚（烯丙胺盐酸盐）包覆金纳米颗粒（PAH Au NPs）上的吸附情况。α-syn以多层形式吸附在PAH Au NPs上，随着α-syn/PAH Au NP比例增加（>2000 α-syn/PAH Au NP），会导致α-syn包覆的PAH Au NPs发生絮凝和沉淀。利用胰蛋白酶消化和圆二色性研究了α-syn在PAH Au NPs上的取向和构象，结果表明α-syn在PAH Au NPs上呈随机取向，β-折叠结构增加，α-螺旋结构减少。无论PAH Au NP浓度如何，还观察到α-syn构象发生了一致的整体变化，这表明结合的α-syn会引发游离α-syn的构象变化。
