title: Structured regions of α-synuclein fibrils include the early-onset Parkinson's disease mutation sites.
abstract: α-Synuclein (AS) fibrils are the major component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD). Here, we use results from an extensive investigation employing solid-state NMR to present a detailed structural characterization and conformational dynamics quantification of full-length AS fibrils. Our results show that the core extends with a repeated structural motif. This result disagrees with the previously proposed fold of AS fibrils obtained with limited solid-state NMR data. Additionally, our results demonstrate that the three single point mutations associated with early-onset PD-A30P, E46K and A53T-are located in structured regions. We find that E46K and A53T mutations, located in rigid β-strands of the wild-type fibrils, are associated with major and minor structural perturbations, respectively.
authors: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors: Gemma
authors: G
authors: Comellas
authors: Luisel R
authors: LR
authors: Lemkau
authors: Andrew J
authors: AJ
authors: Nieuwkoop
authors: Kathryn D
authors: KD
authors: Kloepper
authors: Daniel T
authors: DT
authors: Ladror
authors: Reika
authors: R
authors: Ebisu
authors: Wendy S
authors: WS
authors: Woods
authors: Andrew S
authors: AS
authors: Lipton
authors: Julia M
authors: JM
authors: George
authors: Chad M
authors: CM
authors: Rienstra
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D016631:Lewy Bodies / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein