title: The Parkinson's disease-associated H50Q mutation accelerates α-Synuclein aggregation in vitro.
abstract: α-Synuclein (α-Syn) aggregation is directly linked with Parkinson's disease (PD) pathogenesis. Here, we analyzed the aggregation of newly discovered α-Syn missense mutant H50Q in vitro and found that this mutation significantly accelerates the aggregation and amyloid formation of α-Syn. This mutation, however, did not alter the overall secondary structure as suggested by two-dimensional nuclear magnetic resonance and circular dichroism spectroscopy. The initial oligomerization study by cross-linking and chromatographic techniques suggested that this mutant oligomerizes to an extent similar to that of the wild-type α-Syn protein. Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD.
authors.affiliation: Department of Biosciences and Bioengineering, IIT Bombay , Powai, Mumbai, India 400076.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Ghosh
authors.forename: Mrityunjoy
authors.initials: M
authors.lastname: Mondal
authors.forename: Ganesh M
authors.initials: GM
authors.lastname: Mohite
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.forename: Priyatosh
authors.initials: P
authors.lastname: Ranjan
authors.forename: A
authors.initials: A
authors.lastname: Anoop
authors.forename: Saikat
authors.initials: S
authors.lastname: Ghosh
authors.forename: Narendra Nath
authors.initials: NN
authors.lastname: Jha
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D000682:Amyloid / Q000378:metabolism; D006801:Humans; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein