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Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate

By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self-assembly pathways for the IFQINS hexapeptide, a bio-relevant amyloid former derived from human lysozyme. We verify that (at least) two metastable polymorphic structures exist for this system which are s...

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Detalles Bibliográficos
Autores principales: Zanjani, Ali Asghar Hakami, Reynolds, Nicholas P., Zhang, Afang, Schilling, Tanja, Mezzenga, Raffaele, Berryman, Joshua T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831816/
https://www.ncbi.nlm.nih.gov/pubmed/31690748
http://dx.doi.org/10.1038/s41598-019-52238-x
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author Zanjani, Ali Asghar Hakami
Reynolds, Nicholas P.
Zhang, Afang
Schilling, Tanja
Mezzenga, Raffaele
Berryman, Joshua T.
author_facet Zanjani, Ali Asghar Hakami
Reynolds, Nicholas P.
Zhang, Afang
Schilling, Tanja
Mezzenga, Raffaele
Berryman, Joshua T.
author_sort Zanjani, Ali Asghar Hakami
collection PubMed
description By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self-assembly pathways for the IFQINS hexapeptide, a bio-relevant amyloid former derived from human lysozyme. We verify that (at least) two metastable polymorphic structures exist for this system which are substantially different at the atomistic scale, and compare the conditions under which they are kinetically accessible. We further examine the higher-level polymorphism for these systems at the nanometre to micrometre scales, which is manifested in kinetic differences and in shape differences between structures instead of or as well as differences in the small-scale contact topology. Any future design of structure based inhibitors of the IFQINS steric zipper, or of close homologues such as TFQINS which are likely to have similar structures, should take account of this polymorphic assembly.
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spelling pubmed-68318162019-11-13 Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate Zanjani, Ali Asghar Hakami Reynolds, Nicholas P. Zhang, Afang Schilling, Tanja Mezzenga, Raffaele Berryman, Joshua T. Sci Rep Article By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self-assembly pathways for the IFQINS hexapeptide, a bio-relevant amyloid former derived from human lysozyme. We verify that (at least) two metastable polymorphic structures exist for this system which are substantially different at the atomistic scale, and compare the conditions under which they are kinetically accessible. We further examine the higher-level polymorphism for these systems at the nanometre to micrometre scales, which is manifested in kinetic differences and in shape differences between structures instead of or as well as differences in the small-scale contact topology. Any future design of structure based inhibitors of the IFQINS steric zipper, or of close homologues such as TFQINS which are likely to have similar structures, should take account of this polymorphic assembly. Nature Publishing Group UK 2019-11-05 /pmc/articles/PMC6831816/ /pubmed/31690748 http://dx.doi.org/10.1038/s41598-019-52238-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zanjani, Ali Asghar Hakami
Reynolds, Nicholas P.
Zhang, Afang
Schilling, Tanja
Mezzenga, Raffaele
Berryman, Joshua T.
Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title_full Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title_fullStr Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title_full_unstemmed Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title_short Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate
title_sort kinetic control of parallel versus antiparallel amyloid aggregation via shape of the growing aggregate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831816/
https://www.ncbi.nlm.nih.gov/pubmed/31690748
http://dx.doi.org/10.1038/s41598-019-52238-x
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