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Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers
The most abundant member of the collagen protein family, collagen I (COL1), is composed of two similar (chain A) and one unique (chain B) polypeptides that self-assemble with one amino acid offset into a heterotrimeric triple helix. Given the offset, chain B can occupy either the leading (BAA), midd...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100791/ https://www.ncbi.nlm.nih.gov/pubmed/31907373 http://dx.doi.org/10.1038/s41589-019-0435-y |
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author | Jalan, Abhishek A. Sammon, Douglas Hartgerink, Jeffrey D. Brear, Paul Stott, Katherine Hamaia, Samir W. Hunter, Emma J. Walker, Douglas R. Leitinger, Birgit Farndale, Richard W. |
author_facet | Jalan, Abhishek A. Sammon, Douglas Hartgerink, Jeffrey D. Brear, Paul Stott, Katherine Hamaia, Samir W. Hunter, Emma J. Walker, Douglas R. Leitinger, Birgit Farndale, Richard W. |
author_sort | Jalan, Abhishek A. |
collection | PubMed |
description | The most abundant member of the collagen protein family, collagen I (COL1), is composed of two similar (chain A) and one unique (chain B) polypeptides that self-assemble with one amino acid offset into a heterotrimeric triple helix. Given the offset, chain B can occupy either the leading (BAA), middle (ABA) or trailing (AAB) position of the triple helix, yielding three isomeric biomacromolecules with different protein recognition properties. Despite five decades of intensive research, there is no consensus on the position of chain B in COL1. Here, three triple-helical heterotrimers that each contain a putative Von Willebrand Factor (VWF) and discoidin domain receptor (DDR) recognition sequence from COL1 were designed with chain B permutated in all three positions. AAB demonstrated a strong preference for both VWF and DDR and also induced higher levels of cellular DDR phosphorylation. Thus, we resolve this long-standing mystery and show that COL1 adopts an AAB register. |
format | Online Article Text |
id | pubmed-7100791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-71007912020-07-06 Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers Jalan, Abhishek A. Sammon, Douglas Hartgerink, Jeffrey D. Brear, Paul Stott, Katherine Hamaia, Samir W. Hunter, Emma J. Walker, Douglas R. Leitinger, Birgit Farndale, Richard W. Nat Chem Biol Article The most abundant member of the collagen protein family, collagen I (COL1), is composed of two similar (chain A) and one unique (chain B) polypeptides that self-assemble with one amino acid offset into a heterotrimeric triple helix. Given the offset, chain B can occupy either the leading (BAA), middle (ABA) or trailing (AAB) position of the triple helix, yielding three isomeric biomacromolecules with different protein recognition properties. Despite five decades of intensive research, there is no consensus on the position of chain B in COL1. Here, three triple-helical heterotrimers that each contain a putative Von Willebrand Factor (VWF) and discoidin domain receptor (DDR) recognition sequence from COL1 were designed with chain B permutated in all three positions. AAB demonstrated a strong preference for both VWF and DDR and also induced higher levels of cellular DDR phosphorylation. Thus, we resolve this long-standing mystery and show that COL1 adopts an AAB register. 2020-01-06 2020-04 /pmc/articles/PMC7100791/ /pubmed/31907373 http://dx.doi.org/10.1038/s41589-019-0435-y Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Jalan, Abhishek A. Sammon, Douglas Hartgerink, Jeffrey D. Brear, Paul Stott, Katherine Hamaia, Samir W. Hunter, Emma J. Walker, Douglas R. Leitinger, Birgit Farndale, Richard W. Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title | Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title_full | Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title_fullStr | Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title_full_unstemmed | Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title_short | Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers |
title_sort | chain alignment of collagen i deciphered using computationally designed heterotrimers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100791/ https://www.ncbi.nlm.nih.gov/pubmed/31907373 http://dx.doi.org/10.1038/s41589-019-0435-y |
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