title: The effect of tyrosine residues on α-synuclein fibrillation.
abstract: Aggregation of the intrinsically disordered protein α-synuclein into ordered amyloid fibrils is implicated in the pathogenesis of Parkinson's disease. To unravel the role of Tyr residues in α-synuclein fibrillation, we prepared recombinant N-terminal (Y39A) and C-terminal (Y(125,133,136)A) mutants of α-synuclein and examined their fibrillation propensities by thioflavin T and 1-anilinonaphthalene-8-sulfonate (ANS) fluorescent probes, SDS-PAGE and atomic force microscopy. We demonstrate that in contrast to wild-type α-synuclein, both mutants show large, but comparable delays in the fibrillation process and exhibit enhanced hydrophobicity during fibril-like assembly. Both Tyr mutants form fibril-like structures after prolonged incubation periods, which are morphologically distinct from those of the wild-type protein. Our results suggest that the N-terminal and C-terminal Tyr residues of α-synuclein are important primarily for the initiation of the fibrillation process.
authors.forename: Katja
authors.initials: K
authors.lastname: Pirc
authors.forename: Miha
authors.initials: M
authors.lastname: Škarabot
authors.forename: Lea
authors.initials: L
authors.lastname: Pogačnik
authors.forename: Eva
authors.initials: E
authors.lastname: Žerovnik
authors.forename: Nataša
authors.initials: N
authors.lastname: Poklar-Ulrih
mesh_terms: D006801:Humans; D009154:Mutation / Q000235:genetics; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D014443:Tyrosine