Minimal epitope for Mannitou IgM on ...
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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]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Gimeno, Ana [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Echeverria, Begoña [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Delgado, Sandra [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Semwal, Shubham [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Charro, Diego [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Dansercoer, Ann [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Verstraete, Kenneth [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Azkargorta, Mikel [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
van Noort, Kim [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Wilbers, Ruud H P [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Savvides, Savvas N [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Abrescia, Nicola G A [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Arda, Ana [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Reichardt, Niels C [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine [CIBER-BBN]
Jiménez-Barbero, Jesús [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Serna, Sonia [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Gimeno, Ana [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Echeverria, Begoña [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
Delgado, Sandra [Auteur]
Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Semwal, Shubham [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Charro, Diego [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Dansercoer, Ann [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Verstraete, Kenneth [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Azkargorta, Mikel [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
van Noort, Kim [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Wilbers, Ruud H P [Auteur]
Wageningen University and Research [Wageningen] [WUR]
Savvides, Savvas N [Auteur]
VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC]
Abrescia, Nicola G A [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Arda, Ana [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Reichardt, Niels C [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine [CIBER-BBN]
Jiménez-Barbero, Jesús [Auteur]
Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) [CIC bioGUNE]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Journal title :
Glycobiology
Publisher :
Oxford University Press (OUP)
Publication date :
2021-04-28
ISSN :
1460-2423
English keyword(s) :
core fucose
IgM
Mannitou
N-glycan
paucimannosidic epitopes
IgM
Mannitou
N-glycan
paucimannosidic epitopes
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract
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 ...
Show more >Abstract 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 >
Show more >Abstract 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
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
Computational Molecular Systems Biology
Submission date :
2021-07-08T12:26:24Z
2021-07-12T08:03:28Z
2021-10-08T09:08:29Z
2021-07-12T08:03:28Z
2021-10-08T09:08:29Z
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