title: Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease.
abstract: Alpha-synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.
authors.affiliation: Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University Belfast, UK. o.elagnaf@qub.ac.uk
authors.forename: O M
authors.initials: OM
authors.lastname: El-Agnaf
authors.forename: R
authors.initials: R
authors.lastname: Jakes
authors.forename: M D
authors.initials: MD
authors.lastname: Curran
authors.forename: A
authors.initials: A
authors.lastname: Wallace
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid; D052160:Benzothiazoles; D001704:Biopolymers / Q000378:metabolism; D002942:Circular Dichroism; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016631:Lewy Bodies; D008854:Microscopy, Electron; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D051843:Synucleins; D013844:Thiazoles; D051844:alpha-Synuclein
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D001704:Biopolymers; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051843:Synucleins; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T