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Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain
Amyloid fibrils have been an important subject as they are involved in the development of many amyloidoses and neurodegenerative diseases. The formation of amyloid fibrils is typically initiated by nucleation, whereas its exact mechanisms are largely unknown. With this situation, we have previously...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268647/ https://www.ncbi.nlm.nih.gov/pubmed/35807211 http://dx.doi.org/10.3390/molecules27133964 |
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author | Yoshikawa, Yuki Yuzu, Keisuke Yamamoto, Naoki Morishima, Ken Inoue, Rintaro Sugiyama, Masaaki Iwasaki, Tetsushi So, Masatomo Goto, Yuji Tamura, Atsuo Chatani, Eri |
author_facet | Yoshikawa, Yuki Yuzu, Keisuke Yamamoto, Naoki Morishima, Ken Inoue, Rintaro Sugiyama, Masaaki Iwasaki, Tetsushi So, Masatomo Goto, Yuji Tamura, Atsuo Chatani, Eri |
author_sort | Yoshikawa, Yuki |
collection | PubMed |
description | Amyloid fibrils have been an important subject as they are involved in the development of many amyloidoses and neurodegenerative diseases. The formation of amyloid fibrils is typically initiated by nucleation, whereas its exact mechanisms are largely unknown. With this situation, we have previously identified prefibrillar aggregates in the formation of insulin B chain amyloid fibrils, which have provided an insight into the mechanisms of protein assembly involved in nucleation. Here, we have investigated the formation of insulin B chain amyloid fibrils under different pH conditions to better understand amyloid nucleation mediated by prefibrillar aggregates. The B chain showed strong propensity to form amyloid fibrils over a wide pH range, and prefibrillar aggregates were formed under all examined conditions. In particular, different structures of amyloid fibrils were found at pH 5.2 and pH 8.7, making it possible to compare different pathways. Detailed investigations at pH 5.2 in comparison with those at pH 8.7 have suggested that the evolution of protofibril-like aggregates is a common mechanism. In addition, different processes of evolution of the prefibrillar aggregates have also been identified, suggesting that the nucleation processes diversify depending on the polymorphism of amyloid fibrils. |
format | Online Article Text |
id | pubmed-9268647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92686472022-07-09 Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain Yoshikawa, Yuki Yuzu, Keisuke Yamamoto, Naoki Morishima, Ken Inoue, Rintaro Sugiyama, Masaaki Iwasaki, Tetsushi So, Masatomo Goto, Yuji Tamura, Atsuo Chatani, Eri Molecules Article Amyloid fibrils have been an important subject as they are involved in the development of many amyloidoses and neurodegenerative diseases. The formation of amyloid fibrils is typically initiated by nucleation, whereas its exact mechanisms are largely unknown. With this situation, we have previously identified prefibrillar aggregates in the formation of insulin B chain amyloid fibrils, which have provided an insight into the mechanisms of protein assembly involved in nucleation. Here, we have investigated the formation of insulin B chain amyloid fibrils under different pH conditions to better understand amyloid nucleation mediated by prefibrillar aggregates. The B chain showed strong propensity to form amyloid fibrils over a wide pH range, and prefibrillar aggregates were formed under all examined conditions. In particular, different structures of amyloid fibrils were found at pH 5.2 and pH 8.7, making it possible to compare different pathways. Detailed investigations at pH 5.2 in comparison with those at pH 8.7 have suggested that the evolution of protofibril-like aggregates is a common mechanism. In addition, different processes of evolution of the prefibrillar aggregates have also been identified, suggesting that the nucleation processes diversify depending on the polymorphism of amyloid fibrils. MDPI 2022-06-21 /pmc/articles/PMC9268647/ /pubmed/35807211 http://dx.doi.org/10.3390/molecules27133964 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yoshikawa, Yuki Yuzu, Keisuke Yamamoto, Naoki Morishima, Ken Inoue, Rintaro Sugiyama, Masaaki Iwasaki, Tetsushi So, Masatomo Goto, Yuji Tamura, Atsuo Chatani, Eri Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title | Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title_full | Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title_fullStr | Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title_full_unstemmed | Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title_short | Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain |
title_sort | pathway dependence of the formation and development of prefibrillar aggregates in insulin b chain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268647/ https://www.ncbi.nlm.nih.gov/pubmed/35807211 http://dx.doi.org/10.3390/molecules27133964 |
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