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Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and struct...

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Autores principales: Baiesi, Marco, Orlandini, Enzo, Seno, Flavio, Trovato, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557820/
https://www.ncbi.nlm.nih.gov/pubmed/31182755
http://dx.doi.org/10.1038/s41598-019-44928-3
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author Baiesi, Marco
Orlandini, Enzo
Seno, Flavio
Trovato, Antonio
author_facet Baiesi, Marco
Orlandini, Enzo
Seno, Flavio
Trovato, Antonio
author_sort Baiesi, Marco
collection PubMed
description Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining.
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spelling pubmed-65578202019-06-19 Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding Baiesi, Marco Orlandini, Enzo Seno, Flavio Trovato, Antonio Sci Rep Article Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining. Nature Publishing Group UK 2019-06-10 /pmc/articles/PMC6557820/ /pubmed/31182755 http://dx.doi.org/10.1038/s41598-019-44928-3 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
Baiesi, Marco
Orlandini, Enzo
Seno, Flavio
Trovato, Antonio
Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title_full Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title_fullStr Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title_full_unstemmed Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title_short Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
title_sort sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557820/
https://www.ncbi.nlm.nih.gov/pubmed/31182755
http://dx.doi.org/10.1038/s41598-019-44928-3
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