title: Common structural features of toxic intermediates from α-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging.
abstract: The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed αSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kameda
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Usugi
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Fukui
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Seki
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hongo
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizobata
authors.affiliation: Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.|RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sekiguchi
authors.affiliation: Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.|RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Masaki
authors.affiliation: Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.|RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.|RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Oroguchi
authors.affiliation: Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.|RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakasako
authors.affiliation: RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Koyama-Minami, Tottori 680-8552, Japan kawata@bio.tottori-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawata
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018835:Chaperonin 10 / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D014961:X-Ray Diffraction; D051844:alpha-Synuclein / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D018835:Chaperonin 10; D066329:Protein Aggregates; D051844:alpha-Synuclein
keywords: GroES; XFEL-CXDI; amyloid fibril; toxic intermediate; α-synuclein