Structural Insights into the Molecular Recognition Mechanism of the Cancer and Pathogenic Epitope, LacdiNAc by Immune-Related Lectins.

LacdiNAc glycan-protein interactions hGal-3 hMGL molecular recognition

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
20 May 2021
Historique:
received: 03 03 2021
pubmed: 8 4 2021
medline: 27 5 2021
entrez: 7 4 2021
Statut: ppublish

Résumé

Interactions of glycan-specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, and X-ray crystallography, we investigated the molecular determinants that govern the recognition of the tumour and pathogenic glycobiomarker LacdiNAc (GalNAcβ1-4GlcNAc, LDN), including their comparison with the ubiquitous LacNAc epitope (Galβ1-4GlcNAc, LN), by two human immune-related lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL). A different mechanism of binding and interactions was observed for the hGal-3/LDN and hMGL/LDN complexes, which explains the remarkable difference in the binding specificity of LDN and LN by these two lectins. The new structural clues reported herein are fundamental for the chemical design of mimetics targeting hGal-3/hMGL recognition process.

Identifiants

pubmed: 33826192
doi: 10.1002/chem.202100800
doi:

Substances chimiques

Epitopes 0
Polysaccharides 0
N-acetylgalactosaminyl-1-4-N-acetylglucosamine 136198-41-9
Lactose J2B2A4N98G

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7951-7958

Subventions

Organisme : Fundação para a Ciência e a Tecnologia
ID : IF/00780/2015
Organisme : Fundação para a Ciência e a Tecnologia
ID : PTDC/BIA-MIB/31028/2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : UIDP/04378/2020
Organisme : Fundação para a Ciência e a Tecnologia
ID : UIDB/04378/2020
Organisme : Fundação para a Ciência e a Tecnologia
ID : PD/BD/142847/2018
Organisme : Fundação para a Ciência e a Tecnologia
ID : Project No 22161
Organisme : Fundação para a Ciência e a Tecnologia
ID : RECI/BBB-BEP/0124/2012
Organisme : H2020 European Research Council
ID : ERC-2017-AdG (788143-RECGLYCANMR)
Organisme : Agencia Estatal de Investigación
ID : RTI2018-094751-BC21
Organisme : Agencia Estatal de Investigación
ID : RTI2018-099592-B-C21
Organisme : European Commission
ID : COST 18132 Glyconanoprobes

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Carlos D L Lima (CDL)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Helena Coelho (H)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Ana Gimeno (A)

CIC bioGUNE, Bizkaia, Technology Park, Building 801A, 48170, Derio, Spain.

Filipa Trovão (F)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Ana Diniz (A)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Jorge S Dias (JS)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Jesús Jiménez-Barbero (J)

CIC bioGUNE, Bizkaia, Technology Park, Building 801A, 48170, Derio, Spain.
Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Spain.

Francisco Corzana (F)

Departamento de Quimica, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006, Logroño, Spain.

Ana Luísa Carvalho (AL)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Eurico J Cabrita (EJ)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Filipa Marcelo (F)

UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

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