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Title: Early aggregation preceding the nucleation of insulin amyloid fibrils as monitored by small angle X-ray scattering
Authors: Chatani, Eri
Inoue, Rintaro  kyouindb  KAKEN_id
Imamura, Hiroshi
Sugiyama, Masaaki
Kato, Minoru
Yamamoto, Masahide
Nishida, Koji  kyouindb  KAKEN_id
Kanaya, Toshiji
Author's alias: 井上, 倫太郎
杉山, 正明
西田, 幸次
Issue Date: 27-Oct-2015
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 5
Thesis number: 15485
Abstract: The nucleation event of amyloid fibrils is one of the most crucial processes that dictate the timing and rate of the pathology of diseases; however, information regarding how protein molecules associate to produce fibril nuclei is currently limited. In order to explore this issue in more detail, we performed time-resolved small angle X-ray scattering (SAXS) measurements on insulin fibrillation, in combination with additional multidirectional analyses of thioflavin T fluorescence, FTIR spectroscopy, light scattering, and light transmittance, during the fibrillation process of bovine insulin. SAXS monitoring revealed that insulin molecules associated into rod-like prefibrillar aggregates in the very early stage of the reaction. After the formation of these early aggregates, they appeared to further coalesce mutually to form larger clusters, and the SAXS profiles subsequently showed the further time evolution of conformational development towards mature amyloid fibrils. Distinct types of structural units in terms of shape in a nano-scale order, cross-β content, and thioflavin T fluorescence intensity were observed in a manner that was dependent on the fibrillation pathways. These results suggest the presence of diverse substructures that characterize various fibrillation pathways, and eventually, manifest polymorphisms in mature amyloid fibrils.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/216150
DOI(Published Version): 10.1038/srep15485
PubMed ID: 26503463
Appears in Collections:Journal Articles

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