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Molecular insights into DC-SIGN binding to self-antigens: the interaction with the blood group A/B antigens

Molecular insights into DC-SIGN binding to self-antigens: the interaction with the blood group A/B antigens
Molecular insights into DC-SIGN binding to self-antigens: the interaction with the blood group A/B antigens
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 LeX. 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 LeX. 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 Ca2+ 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.
1554-8929
1660-1671
Valverde, Pablo
34a79a7c-562e-4c8a-92b9-b17d1275ef9a
Delgado, Sandra
50db02aa-4878-4d73-be72-634179f07fc6
Martínez, J. Daniel
0adf4f69-ac2d-4e8d-9527-fba136ee2a15
Vendeville, Jean
9f2c6155-cf23-4733-9402-33633fb5bb47
Malassis, Julien G.J.
5cd4224d-e4db-4835-863c-56b709511ccd
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Reichardt, Niels C.
00b4a72e-ca65-4ea8-a28c-deb3d8ec65fd
Cañada Vicinay, F. Javier
1a2325f8-07d7-4979-afa5-81c6beee1653
Jiménez-Barbero, Jesús
8d249106-a8a2-40ff-bcf0-e16ee3b75d32
Ardá, Ana
381d3f7d-6c5a-427a-8433-bdfc02da3a6d
Valverde, Pablo
34a79a7c-562e-4c8a-92b9-b17d1275ef9a
Delgado, Sandra
50db02aa-4878-4d73-be72-634179f07fc6
Martínez, J. Daniel
0adf4f69-ac2d-4e8d-9527-fba136ee2a15
Vendeville, Jean
9f2c6155-cf23-4733-9402-33633fb5bb47
Malassis, Julien G.J.
5cd4224d-e4db-4835-863c-56b709511ccd
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Reichardt, Niels C.
00b4a72e-ca65-4ea8-a28c-deb3d8ec65fd
Cañada Vicinay, F. Javier
1a2325f8-07d7-4979-afa5-81c6beee1653
Jiménez-Barbero, Jesús
8d249106-a8a2-40ff-bcf0-e16ee3b75d32
Ardá, Ana
381d3f7d-6c5a-427a-8433-bdfc02da3a6d

Valverde, Pablo, Delgado, Sandra, Martínez, J. Daniel, Vendeville, Jean, Malassis, Julien G.J., Linclau, Bruno, Reichardt, Niels C., Cañada Vicinay, F. Javier, Jiménez-Barbero, Jesús and Ardá, Ana (2019) Molecular insights into DC-SIGN binding to self-antigens: the interaction with the blood group A/B antigens. ACS Chemical Biology, 14 (7), 1660-1671. (doi:10.1021/acschembio.9b00458).

Record type: Article

Abstract

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 LeX. 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 LeX. 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 Ca2+ 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.

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Manuscript_DCSIGN_FINAL_revised_v2 - Accepted Manuscript
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Accepted/In Press date: 25 June 2019
e-pub ahead of print date: 25 June 2019

Identifiers

Local EPrints ID: 432537
URI: http://eprints.soton.ac.uk/id/eprint/432537
ISSN: 1554-8929
PURE UUID: ffedb748-31ae-4500-a3b4-d2f5ab0a3a31
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

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Date deposited: 17 Jul 2019 16:30
Last modified: 10 Jan 2022 06:22

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Contributors

Author: Pablo Valverde
Author: Sandra Delgado
Author: J. Daniel Martínez
Author: Jean Vendeville
Author: Julien G.J. Malassis
Author: Bruno Linclau ORCID iD
Author: Niels C. Reichardt
Author: F. Javier Cañada Vicinay
Author: Jesús Jiménez-Barbero
Author: Ana Ardá

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