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Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates

Insulin rapidly fibrillates in the presence of amyloid seeds from different sources. To address its cross-reactivity we chose the seeds of seven model proteins and peptides along with the seeds of insulin itself. Model candidates were selected/designed according to their size, amino acid sequence, a...

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Autores principales: Akbarian, Mohsen, Kianpour, Maryam, Yousefi, Reza, Moosavi-Movahedi, Ali Akbar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056291/
https://www.ncbi.nlm.nih.gov/pubmed/35518209
http://dx.doi.org/10.1039/d0ra05414c
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author Akbarian, Mohsen
Kianpour, Maryam
Yousefi, Reza
Moosavi-Movahedi, Ali Akbar
author_facet Akbarian, Mohsen
Kianpour, Maryam
Yousefi, Reza
Moosavi-Movahedi, Ali Akbar
author_sort Akbarian, Mohsen
collection PubMed
description Insulin rapidly fibrillates in the presence of amyloid seeds from different sources. To address its cross-reactivity we chose the seeds of seven model proteins and peptides along with the seeds of insulin itself. Model candidates were selected/designed according to their size, amino acid sequence, and hydrophobicity. We found while some seeds provided catalytic ends for inducing the formation of non-native insulin conformers and increase fibrillation, others attenuated insulin fibrillation kinetics. We also observed competition between the intermediate insulin conformers which formed with urea and amyloid seeds in entering the fibrillogenic pathway. Simultaneous incubation of insulin with urea and amyloid seeds resulted in the formation of nearly similar insulin intermediate conformers which synergistically enhance insulin fibrillation kinetics. Given these results, it is highly likely that, structurally, there is a specific intermediate in different pathways of insulin fibrillation that governs fibrillation kinetics and morphology of the final mature fibril. Overall, this study provides a novel mechanistic insight into insulin fibrillation and gives new information on how seeds of different proteins are capable of altering insulin fibrillation kinetics and morphology. This report, for the first time, tries to answer an important question that why fibrillation of insulin is either accelerated or attenuated in the presence of amyloid fibril seeds from different sources.
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spelling pubmed-90562912022-05-04 Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates Akbarian, Mohsen Kianpour, Maryam Yousefi, Reza Moosavi-Movahedi, Ali Akbar RSC Adv Chemistry Insulin rapidly fibrillates in the presence of amyloid seeds from different sources. To address its cross-reactivity we chose the seeds of seven model proteins and peptides along with the seeds of insulin itself. Model candidates were selected/designed according to their size, amino acid sequence, and hydrophobicity. We found while some seeds provided catalytic ends for inducing the formation of non-native insulin conformers and increase fibrillation, others attenuated insulin fibrillation kinetics. We also observed competition between the intermediate insulin conformers which formed with urea and amyloid seeds in entering the fibrillogenic pathway. Simultaneous incubation of insulin with urea and amyloid seeds resulted in the formation of nearly similar insulin intermediate conformers which synergistically enhance insulin fibrillation kinetics. Given these results, it is highly likely that, structurally, there is a specific intermediate in different pathways of insulin fibrillation that governs fibrillation kinetics and morphology of the final mature fibril. Overall, this study provides a novel mechanistic insight into insulin fibrillation and gives new information on how seeds of different proteins are capable of altering insulin fibrillation kinetics and morphology. This report, for the first time, tries to answer an important question that why fibrillation of insulin is either accelerated or attenuated in the presence of amyloid fibril seeds from different sources. The Royal Society of Chemistry 2020-08-13 /pmc/articles/PMC9056291/ /pubmed/35518209 http://dx.doi.org/10.1039/d0ra05414c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Akbarian, Mohsen
Kianpour, Maryam
Yousefi, Reza
Moosavi-Movahedi, Ali Akbar
Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title_full Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title_fullStr Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title_full_unstemmed Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title_short Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
title_sort characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056291/
https://www.ncbi.nlm.nih.gov/pubmed/35518209
http://dx.doi.org/10.1039/d0ra05414c
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