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A cysteine-based molecular code informs collagen C-propeptide assembly
Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor g...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181919/ https://www.ncbi.nlm.nih.gov/pubmed/30310058 http://dx.doi.org/10.1038/s41467-018-06185-2 |
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author | DiChiara, Andrew S. Li, Rasia C. Suen, Patreece H. Hosseini, Azade S. Taylor, Rebecca J. Weickhardt, Alexander F. Malhotra, Diya McCaslin, Darrell R. Shoulders, Matthew D. |
author_facet | DiChiara, Andrew S. Li, Rasia C. Suen, Patreece H. Hosseini, Azade S. Taylor, Rebecca J. Weickhardt, Alexander F. Malhotra, Diya McCaslin, Darrell R. Shoulders, Matthew D. |
author_sort | DiChiara, Andrew S. |
collection | PubMed |
description | Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca(2+) in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms. |
format | Online Article Text |
id | pubmed-6181919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61819192018-10-15 A cysteine-based molecular code informs collagen C-propeptide assembly DiChiara, Andrew S. Li, Rasia C. Suen, Patreece H. Hosseini, Azade S. Taylor, Rebecca J. Weickhardt, Alexander F. Malhotra, Diya McCaslin, Darrell R. Shoulders, Matthew D. Nat Commun Article Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca(2+) in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms. Nature Publishing Group UK 2018-10-11 /pmc/articles/PMC6181919/ /pubmed/30310058 http://dx.doi.org/10.1038/s41467-018-06185-2 Text en © The Author(s) 2018 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 DiChiara, Andrew S. Li, Rasia C. Suen, Patreece H. Hosseini, Azade S. Taylor, Rebecca J. Weickhardt, Alexander F. Malhotra, Diya McCaslin, Darrell R. Shoulders, Matthew D. A cysteine-based molecular code informs collagen C-propeptide assembly |
title | A cysteine-based molecular code informs collagen C-propeptide assembly |
title_full | A cysteine-based molecular code informs collagen C-propeptide assembly |
title_fullStr | A cysteine-based molecular code informs collagen C-propeptide assembly |
title_full_unstemmed | A cysteine-based molecular code informs collagen C-propeptide assembly |
title_short | A cysteine-based molecular code informs collagen C-propeptide assembly |
title_sort | cysteine-based molecular code informs collagen c-propeptide assembly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181919/ https://www.ncbi.nlm.nih.gov/pubmed/30310058 http://dx.doi.org/10.1038/s41467-018-06185-2 |
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