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Cis-trans isomerization of peptoid residues in the collagen triple-helix
Cis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be tran...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663571/ https://www.ncbi.nlm.nih.gov/pubmed/37989738 http://dx.doi.org/10.1038/s41467-023-43469-8 |
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author | Qiu, Rongmao Li, Xiaojing Huang, Kui Bai, Weizhe Zhou, Daoning Li, Gang Qin, Zhao Li, Yang |
author_facet | Qiu, Rongmao Li, Xiaojing Huang, Kui Bai, Weizhe Zhou, Daoning Li, Gang Qin, Zhao Li, Yang |
author_sort | Qiu, Rongmao |
collection | PubMed |
description | Cis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be trans to form its hallmark triple-helix structure. Here, using host-guest collagen mimetic peptides (CMPs), we discover that surprisingly, even the cis-enforcing peptoid residues (N-substituted glycines) form stable triple-helices. Our interrogations establish that these peptoid residues entropically stabilize the triple-helix by pre-organizing individual peptides into a polyproline-II helix. Moreover, noting that the cis-demanding peptoid residues drastically reduce the folding rate, we design a CMP whose triple-helix formation can be controlled by peptoid cis-trans isomerization, enabling direct targeting of fibrotic remodeling in myocardial infarction in vivo. These findings elucidate the principles of peptoid cis-trans isomerization in protein folding and showcase the exploitation of cis-amide-favoring residues in building programmable and functional peptidomimetics. |
format | Online Article Text |
id | pubmed-10663571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106635712023-11-21 Cis-trans isomerization of peptoid residues in the collagen triple-helix Qiu, Rongmao Li, Xiaojing Huang, Kui Bai, Weizhe Zhou, Daoning Li, Gang Qin, Zhao Li, Yang Nat Commun Article Cis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be trans to form its hallmark triple-helix structure. Here, using host-guest collagen mimetic peptides (CMPs), we discover that surprisingly, even the cis-enforcing peptoid residues (N-substituted glycines) form stable triple-helices. Our interrogations establish that these peptoid residues entropically stabilize the triple-helix by pre-organizing individual peptides into a polyproline-II helix. Moreover, noting that the cis-demanding peptoid residues drastically reduce the folding rate, we design a CMP whose triple-helix formation can be controlled by peptoid cis-trans isomerization, enabling direct targeting of fibrotic remodeling in myocardial infarction in vivo. These findings elucidate the principles of peptoid cis-trans isomerization in protein folding and showcase the exploitation of cis-amide-favoring residues in building programmable and functional peptidomimetics. Nature Publishing Group UK 2023-11-21 /pmc/articles/PMC10663571/ /pubmed/37989738 http://dx.doi.org/10.1038/s41467-023-43469-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Qiu, Rongmao Li, Xiaojing Huang, Kui Bai, Weizhe Zhou, Daoning Li, Gang Qin, Zhao Li, Yang Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title | Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title_full | Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title_fullStr | Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title_full_unstemmed | Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title_short | Cis-trans isomerization of peptoid residues in the collagen triple-helix |
title_sort | cis-trans isomerization of peptoid residues in the collagen triple-helix |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663571/ https://www.ncbi.nlm.nih.gov/pubmed/37989738 http://dx.doi.org/10.1038/s41467-023-43469-8 |
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