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Evolution and folding of repeat proteins
Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. These proteins constitute excellent model systems to investigate how evolution relates to structure, folding, and function. Here, we propose a scheme to map evolutionary information at...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351489/ https://www.ncbi.nlm.nih.gov/pubmed/35905321 http://dx.doi.org/10.1073/pnas.2204131119 |
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author | Galpern, Ezequiel A. Marchi, Jacopo Mora, Thierry Walczak, Aleksandra M. Ferreiro, Diego U. |
author_facet | Galpern, Ezequiel A. Marchi, Jacopo Mora, Thierry Walczak, Aleksandra M. Ferreiro, Diego U. |
author_sort | Galpern, Ezequiel A. |
collection | PubMed |
description | Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. These proteins constitute excellent model systems to investigate how evolution relates to structure, folding, and function. Here, we propose a scheme to map evolutionary information at the sequence level to a coarse-grained model for repeat-protein folding and use it to investigate the folding of thousands of repeat proteins. We model the energetics by a combination of an inverse Potts-model scheme with an explicit mechanistic model of duplications and deletions of repeats to calculate the evolutionary parameters of the system at the single-residue level. These parameters are used to inform an Ising-like model that allows for the generation of folding curves, apparent domain emergence, and occupation of intermediate states that are highly compatible with experimental data in specific case studies. We analyzed the folding of thousands of natural Ankyrin repeat proteins and found that a multiplicity of folding mechanisms are possible. Fully cooperative all-or-none transitions are obtained for arrays with enough sequence-similar elements and strong interactions between them, while noncooperative element-by-element intermittent folding arose if the elements are dissimilar and the interactions between them are energetically weak. Additionally, we characterized nucleation-propagation and multidomain folding mechanisms. We show that the global stability and cooperativity of the repeating arrays can be predicted from simple sequence scores. |
format | Online Article Text |
id | pubmed-9351489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-93514892023-01-29 Evolution and folding of repeat proteins Galpern, Ezequiel A. Marchi, Jacopo Mora, Thierry Walczak, Aleksandra M. Ferreiro, Diego U. Proc Natl Acad Sci U S A Biological Sciences Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. These proteins constitute excellent model systems to investigate how evolution relates to structure, folding, and function. Here, we propose a scheme to map evolutionary information at the sequence level to a coarse-grained model for repeat-protein folding and use it to investigate the folding of thousands of repeat proteins. We model the energetics by a combination of an inverse Potts-model scheme with an explicit mechanistic model of duplications and deletions of repeats to calculate the evolutionary parameters of the system at the single-residue level. These parameters are used to inform an Ising-like model that allows for the generation of folding curves, apparent domain emergence, and occupation of intermediate states that are highly compatible with experimental data in specific case studies. We analyzed the folding of thousands of natural Ankyrin repeat proteins and found that a multiplicity of folding mechanisms are possible. Fully cooperative all-or-none transitions are obtained for arrays with enough sequence-similar elements and strong interactions between them, while noncooperative element-by-element intermittent folding arose if the elements are dissimilar and the interactions between them are energetically weak. Additionally, we characterized nucleation-propagation and multidomain folding mechanisms. We show that the global stability and cooperativity of the repeating arrays can be predicted from simple sequence scores. National Academy of Sciences 2022-07-29 2022-08-02 /pmc/articles/PMC9351489/ /pubmed/35905321 http://dx.doi.org/10.1073/pnas.2204131119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Galpern, Ezequiel A. Marchi, Jacopo Mora, Thierry Walczak, Aleksandra M. Ferreiro, Diego U. Evolution and folding of repeat proteins |
title | Evolution and folding of repeat proteins |
title_full | Evolution and folding of repeat proteins |
title_fullStr | Evolution and folding of repeat proteins |
title_full_unstemmed | Evolution and folding of repeat proteins |
title_short | Evolution and folding of repeat proteins |
title_sort | evolution and folding of repeat proteins |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351489/ https://www.ncbi.nlm.nih.gov/pubmed/35905321 http://dx.doi.org/10.1073/pnas.2204131119 |
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