Title :

Minimal epitope for Mannitou IgM on paucimannose-carrying glycoproteins

Author(s) :

Robakiewicz, Stefania [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Serna, Sonia [Auteur]
Gimeno, Ana [Auteur]
Echeverria, Begoña [Auteur]
Delgado, Sandra [Auteur]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Semwal, Shubham [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Charro, Diego [Auteur]
Dansercoer, Ann [Auteur]
Verstraete, Kenneth [Auteur]
Azkargorta, Mikel [Auteur]
van Noort, Kim [Auteur]
Wilbers, Ruud H P [Auteur]
Savvides, Savvas N [Auteur]
Abrescia, Nicola G A [Auteur]
Arda, Ana [Auteur]
Reichardt, Niels C [Auteur]
Jiménez-Barbero, Jesús [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Reichardt, Niels C [Auteur]

Journal title :

Glycobiology

Volume number :

31

Pages :

1005-1017

Publisher :

Oxford University Press (OUP)

Publication date :

2021-04-28

ISSN :

1460-2423

English keyword(s) :

core fucose
IgM
Mannitou
N-glycan
paucimannosidic epitopes

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Paucimannosidic glycans are restricted to the core structure [Man1–3GlcNAc2Fuc0–1] of N-glycans and are rarely found in mammalian tissues. Yet, especially [Man2-3GlcNAc2Fuc1] have been found significantly upregulated in ...
Show more >Paucimannosidic glycans are restricted to the core structure [Man1–3GlcNAc2Fuc0–1] of N-glycans and are rarely found in mammalian tissues. Yet, especially [Man2-3GlcNAc2Fuc1] have been found significantly upregulated in tumors, including in colorectal and liver cancer. Mannitou IgM is a murine monoclonal antibody that was previously shown to recognize Man3GlcNAc2 with an almost exclusive selectivity. Here, we have sought the definition of the minimal glycan epitope of Mannitou IgM, initiated by screening on a newly designed paucimannosidic glycan microarray; among the best binders were Man3GlcNAc2 and its α1,6 core-fucosylated variant, Man3GlcNAc2Fuc1. Unexpectedly and in contrast to earlier findings, Man5GlcNAc2-type structures bind equally well and a large tolerance was observed for substitutions on the α1,6 arm. It was confirmed that any substitution on the single α1,3-linked mannose completely abolishes binding. Surface plasmon resonance for kinetic measurements of Mannitou IgM binding, either directly on the glycans or as presented on omega-1 and kappa-5 soluble egg antigens from the helminth parasite Schistosoma mansoni, showed submicromolar affinities. To characterize the epitope in greater and atomic detail, saturation transfer difference nuclear magnetic resonance spectroscopy was performed with the Mannitou antigen-binding fragment. The STD-NMR data demonstrated the strongest interactions with the aliphatic protons H1 and H2 of the α1–3-linked mannose and weaker imprints on its H3, H4 and H5 protons. In conclusion, Mannitou IgM binding requires a nonsubstituted α1,3-linked mannose branch of paucimannose also on proteins, making it a highly specific tool for the distinction of concurrent human tumor-associated carbohydrate antigens.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Computational Molecular Systems Biology

Submission date :

2021-10-14T13:00:39Z
2021-10-18T07:36:43Z