Minimal epitope for Mannitou IgM on paucimannose-carrying glycoproteins

Autor: Ana Gimeno, Jesús Jiménez-Barbero, Stefania Robakiewicz, Sandra Delgado, Clarisse Bridot, Begoña Echeverria, Ann Dansercoer, Nicola G. A. Abrescia, Jérôme de Ruyck, Sonia Serna, Shubham Semwal, Mikel Azkargorta, Ruud H. P. Wilbers, Ana Ardá, Savvas N. Savvides, Diego Charro, Niels C. Reichardt, Kenneth Verstraete, Julie Bouckaert, Kim van Noort
Přispěvatelé: Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centro de Investigación Cooperativa en Biomateriales (CIC biomaGUNE), Cell Biology and Stem Cells Unit (CICbioGUNE), Technologic Park of Bizkaia, VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Wageningen University and Research [Wageningen] (WUR), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE], Cell Biology and Stem Cells Unit [CICbioGUNE], VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC], Wageningen University and Research [Wageningen] [WUR], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine [CIBER-BBN]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
[SDV]Life Sciences [q-bio]
Mannose
Biochemistry
Epitope
Epitopes
Mice
chemistry.chemical_compound
0302 clinical medicine
Mannitou
N-linked glycosylation
BINDING
Medicine and Health Sciences
AFFINITY
Mammals
chemistry.chemical_classification
0303 health sciences
biology
PROLIFERATION
paucimannosidic epitopes
Schistosoma mansoni
N-GLYCOSYLATION
CANCER
3. Good health
DNA-Binding Proteins
GLYCAN MICROARRAYS
030220 oncology & carcinogenesis
N-glycan
Antibody
Glycan
core fucose
IgM
CORE FUCOSYLATION
03 medical and health sciences
Antigen
Polysaccharides
Animals
Humans
Laboratorium voor Nematologie
Fucose
Glycoproteins
030304 developmental biology
Membrane Proteins
Biology and Life Sciences
IgM binding
Immunoglobulin M
chemistry
ANTIBODIES
biology.protein
Laboratory of Nematology
Glycoprotein
ELASTASE
Zdroj: Glycobiology
Glycobiology, Oxford University Press (OUP), 2021, Glycobiology, ⟨10.1093/glycob/cwab027⟩
Glycobiology, Oxford University Press (OUP), 2021, Glycobiology
Glycobiology, 31(8), 1005-1017
Glycobiology, 2021, Glycobiology
Glycobiology 31 (2021) 8
GLYCOBIOLOGY
HAL
ISSN: 0959-6658
1460-2423
DOI: 10.1093/glycob/cwab027⟩
Popis: 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.
Databáze: OpenAIRE
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