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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6831816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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