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Molecular Insights into DC-SIGN Binding to Self-Antigens: The Interaction with the Blood Group A/B Antigens
[Image: see text] The dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important receptor of the immune system. Besides its role as pathogen recognition receptor (PRR), it also interacts with endogenous glycoproteins through the specific recognition of s...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646960/ https://www.ncbi.nlm.nih.gov/pubmed/31283166 http://dx.doi.org/10.1021/acschembio.9b00458 |
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author | Valverde, Pablo Delgado, Sandra Martínez, J. Daniel Vendeville, Jean-Baptiste Malassis, Julien Linclau, Bruno Reichardt, Niels-Christian Cañada, Francisco Javier Jiménez-Barbero, Jesús Ardá, Ana |
author_facet | Valverde, Pablo Delgado, Sandra Martínez, J. Daniel Vendeville, Jean-Baptiste Malassis, Julien Linclau, Bruno Reichardt, Niels-Christian Cañada, Francisco Javier Jiménez-Barbero, Jesús Ardá, Ana |
author_sort | Valverde, Pablo |
collection | PubMed |
description | [Image: see text] The dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important receptor of the immune system. Besides its role as pathogen recognition receptor (PRR), it also interacts with endogenous glycoproteins through the specific recognition of self-glycan epitopes, like Le(X). However, this lectin represents a paradigmatic case of glycan binding promiscuity, and it also has been shown to recognize antigens with α1−α2 linked fucose, such as the histo blood group antigens, with similar affinities to Le(X). Herein, we have studied the interaction in solution between DC-SIGN and the blood group A and B antigens, to get insights into the atomic details of such interaction. With a combination of different NMR experiments, we demonstrate that the Fuc coordinates the primary Ca(2+) ion with a single binding mode through 3-OH and 4-OH. The terminal αGal/αGalNAc affords marginal direct polar contacts with the protein, but provides a hydrophobic hook in which V351 of the lectin perfectly fits. Moreover, we have found that αGal, but not αGalNAc, is a weak binder itself for DC-SIGN, which could endow an additional binding mode for the blood group B antigen, but not for blood group A. |
format | Online Article Text |
id | pubmed-6646960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-66469602019-07-24 Molecular Insights into DC-SIGN Binding to Self-Antigens: The Interaction with the Blood Group A/B Antigens Valverde, Pablo Delgado, Sandra Martínez, J. Daniel Vendeville, Jean-Baptiste Malassis, Julien Linclau, Bruno Reichardt, Niels-Christian Cañada, Francisco Javier Jiménez-Barbero, Jesús Ardá, Ana ACS Chem Biol [Image: see text] The dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important receptor of the immune system. Besides its role as pathogen recognition receptor (PRR), it also interacts with endogenous glycoproteins through the specific recognition of self-glycan epitopes, like Le(X). However, this lectin represents a paradigmatic case of glycan binding promiscuity, and it also has been shown to recognize antigens with α1−α2 linked fucose, such as the histo blood group antigens, with similar affinities to Le(X). Herein, we have studied the interaction in solution between DC-SIGN and the blood group A and B antigens, to get insights into the atomic details of such interaction. With a combination of different NMR experiments, we demonstrate that the Fuc coordinates the primary Ca(2+) ion with a single binding mode through 3-OH and 4-OH. The terminal αGal/αGalNAc affords marginal direct polar contacts with the protein, but provides a hydrophobic hook in which V351 of the lectin perfectly fits. Moreover, we have found that αGal, but not αGalNAc, is a weak binder itself for DC-SIGN, which could endow an additional binding mode for the blood group B antigen, but not for blood group A. American Chemical Society 2019-06-25 2019-07-19 /pmc/articles/PMC6646960/ /pubmed/31283166 http://dx.doi.org/10.1021/acschembio.9b00458 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Valverde, Pablo Delgado, Sandra Martínez, J. Daniel Vendeville, Jean-Baptiste Malassis, Julien Linclau, Bruno Reichardt, Niels-Christian Cañada, Francisco Javier Jiménez-Barbero, Jesús Ardá, Ana Molecular Insights into DC-SIGN Binding to Self-Antigens: The Interaction with the Blood Group A/B Antigens |
title | Molecular Insights into DC-SIGN Binding to Self-Antigens:
The Interaction with the Blood Group A/B Antigens |
title_full | Molecular Insights into DC-SIGN Binding to Self-Antigens:
The Interaction with the Blood Group A/B Antigens |
title_fullStr | Molecular Insights into DC-SIGN Binding to Self-Antigens:
The Interaction with the Blood Group A/B Antigens |
title_full_unstemmed | Molecular Insights into DC-SIGN Binding to Self-Antigens:
The Interaction with the Blood Group A/B Antigens |
title_short | Molecular Insights into DC-SIGN Binding to Self-Antigens:
The Interaction with the Blood Group A/B Antigens |
title_sort | molecular insights into dc-sign binding to self-antigens:
the interaction with the blood group a/b antigens |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646960/ https://www.ncbi.nlm.nih.gov/pubmed/31283166 http://dx.doi.org/10.1021/acschembio.9b00458 |
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