@article{9f4f2d65202e405cb06b040b728dbdc7,
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 aSyn 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.",
keywords = "Amyloid fibril, GroES, Toxic intermediate, XFEL-CXDI, α-synuclein",
author = "Hiroshi Kameda and Sayaka Usugi and Mana Kobayashi and Naoya Fukui and Seki Lee and Kunihiro Hongo and Tomohiro Mizobata and Yuki Sekiguchi and Yu Masaki and Amane Kobayashi and Tomotaka Oroguchi and Masayoshi Nakasako and Yuki Takayama and Masaki Yamamoto and Yasushi Kawata",
note = "Funding Information: The authors thank Ms. E. Kawahara of Tottori University for technical assistance in measurements of electron microscopy. The authors also thank to Dr. Kensuke Tono, Dr. Yuichi Inubushi, Dr. Takashi Kameshima, and Dr. Yasumasa Joti of JASRI, and Mr. Tetsukon Kim, Mr. Takahiro Date, Mr. Toshiyuki Murakami and the other members of the Engineering Team of the SACLA for their help in the alignment of the optics, and our apparatus. This study was supported by the X-Ray Free Electron Laser Priority Strategy Program to Y.K., M.N. and M.Y. from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The specimen preparation and software development in this study is also supported in part by a Grant-in-Aid for Scientific Research (C) (No. jp25440027 to Y.K., and Nos. jp1920402, jp22018027 and jp2465414 to M.N.), a Grant-in-Aid for Research Activity start-up (No. jp25891033 to Y.T.) from the Japan Society for the Promotion of Science, and a Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT (No. jp24113716 to Y.K., Nos. jp15076210, jp23120525, jp25120725 to M.N. and No. jp24113723 to T.O.). Y.T. was employed by the RIKEN Special Postdoctoral Researchers Program. The XFEL-CXDI diffraction data for structure analyses were collected at SACLA (proposal Nos. 2013A8043, 2013B8049 and 2014A8033). The phaseretrieval calculations and multivariate analyses were performed using the mini-K supercomputer system at the SACLA facility. Publisher Copyright: {\textcopyright} The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.",
year = "2017",
month = jan,
day = "1",
doi = "10.1093/jb/mvw052",
language = "English",
volume = "161",
pages = "55--65",
journal = "Journal of Biochemistry",
issn = "0021-924X",
publisher = "Oxford University Press",
number = "1",
}