title: α-Synuclein's adsorption, conformation, and orientation on cationic gold nanoparticle surfaces seeds global conformation change.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Jie An
authors.initials: JA
authors.lastname: Yang
authors.forename: Wayne
authors.initials: W
authors.lastname: Lin
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Woods
authors.forename: Julia M
authors.initials: JM
authors.lastname: George
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Murphy
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D053768:Metal Nanoparticles / Q000737:chemistry*; D008969:Molecular Sequence Data; D011073:Polyamines / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D013499:Surface Properties; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011073:Polyamines; D011994:Recombinant Proteins; D051844:alpha-Synuclein; C063994:polyallylamine; D006046:Gold