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Tying up the Loose Ends: A Mathematically Knotted Protein
Knots have attracted scientists in mathematics, physics, biology, and engineering. Long flexible thin strings easily knot and tangle as experienced in our daily life. Similarly, long polymer chains inevitably tend to get trapped into knots. Little is known about their formation or function in protei...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182377/ https://www.ncbi.nlm.nih.gov/pubmed/34109153 http://dx.doi.org/10.3389/fchem.2021.663241 |
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author | Hsu, Shang-Te Danny Lee, Yun-Tzai Cloud Mikula, Kornelia M. Backlund, Sofia M. Tascón, Igor Goldman, Adrian Iwaï, Hideo |
author_facet | Hsu, Shang-Te Danny Lee, Yun-Tzai Cloud Mikula, Kornelia M. Backlund, Sofia M. Tascón, Igor Goldman, Adrian Iwaï, Hideo |
author_sort | Hsu, Shang-Te Danny |
collection | PubMed |
description | Knots have attracted scientists in mathematics, physics, biology, and engineering. Long flexible thin strings easily knot and tangle as experienced in our daily life. Similarly, long polymer chains inevitably tend to get trapped into knots. Little is known about their formation or function in proteins despite >1,000 knotted proteins identified in nature. However, these protein knots are not mathematical knots with their backbone polypeptide chains because of their open termini, and the presence of a “knot” depends on the algorithm used to create path closure. Furthermore, it is generally not possible to control the topology of the unfolded states of proteins, therefore making it challenging to characterize functional and physicochemical properties of knotting in any polymer. Covalently linking the amino and carboxyl termini of the deeply trefoil-knotted YibK from Pseudomonas aeruginosa allowed us to create the truly backbone knotted protein by enzymatic peptide ligation. Moreover, we produced and investigated backbone cyclized YibK without any knotted structure. Thus, we could directly probe the effect of the backbone knot and the decrease in conformational entropy on protein folding. The backbone cyclization did not perturb the native structure and its cofactor binding affinity, but it substantially increased the thermal stability and reduced the aggregation propensity. The enhanced stability of a backbone knotted YibK could be mainly originated from an increased ruggedness of its free energy landscape and the destabilization of the denatured state by backbone cyclization with little contribution from a knot structure. Despite the heterogeneity in the side-chain compositions, the chemically unfolded cyclized YibK exhibited several macroscopic physico-chemical attributes that agree with theoretical predictions derived from polymer physics. |
format | Online Article Text |
id | pubmed-8182377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81823772021-06-08 Tying up the Loose Ends: A Mathematically Knotted Protein Hsu, Shang-Te Danny Lee, Yun-Tzai Cloud Mikula, Kornelia M. Backlund, Sofia M. Tascón, Igor Goldman, Adrian Iwaï, Hideo Front Chem Chemistry Knots have attracted scientists in mathematics, physics, biology, and engineering. Long flexible thin strings easily knot and tangle as experienced in our daily life. Similarly, long polymer chains inevitably tend to get trapped into knots. Little is known about their formation or function in proteins despite >1,000 knotted proteins identified in nature. However, these protein knots are not mathematical knots with their backbone polypeptide chains because of their open termini, and the presence of a “knot” depends on the algorithm used to create path closure. Furthermore, it is generally not possible to control the topology of the unfolded states of proteins, therefore making it challenging to characterize functional and physicochemical properties of knotting in any polymer. Covalently linking the amino and carboxyl termini of the deeply trefoil-knotted YibK from Pseudomonas aeruginosa allowed us to create the truly backbone knotted protein by enzymatic peptide ligation. Moreover, we produced and investigated backbone cyclized YibK without any knotted structure. Thus, we could directly probe the effect of the backbone knot and the decrease in conformational entropy on protein folding. The backbone cyclization did not perturb the native structure and its cofactor binding affinity, but it substantially increased the thermal stability and reduced the aggregation propensity. The enhanced stability of a backbone knotted YibK could be mainly originated from an increased ruggedness of its free energy landscape and the destabilization of the denatured state by backbone cyclization with little contribution from a knot structure. Despite the heterogeneity in the side-chain compositions, the chemically unfolded cyclized YibK exhibited several macroscopic physico-chemical attributes that agree with theoretical predictions derived from polymer physics. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8182377/ /pubmed/34109153 http://dx.doi.org/10.3389/fchem.2021.663241 Text en Copyright © 2021 Hsu, Lee, Mikula, Backlund, Tascón, Goldman and Iwaï. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Hsu, Shang-Te Danny Lee, Yun-Tzai Cloud Mikula, Kornelia M. Backlund, Sofia M. Tascón, Igor Goldman, Adrian Iwaï, Hideo Tying up the Loose Ends: A Mathematically Knotted Protein |
title | Tying up the Loose Ends: A Mathematically Knotted Protein |
title_full | Tying up the Loose Ends: A Mathematically Knotted Protein |
title_fullStr | Tying up the Loose Ends: A Mathematically Knotted Protein |
title_full_unstemmed | Tying up the Loose Ends: A Mathematically Knotted Protein |
title_short | Tying up the Loose Ends: A Mathematically Knotted Protein |
title_sort | tying up the loose ends: a mathematically knotted protein |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182377/ https://www.ncbi.nlm.nih.gov/pubmed/34109153 http://dx.doi.org/10.3389/fchem.2021.663241 |
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