TY - JOUR
T1 - Structural Insights into the Molecular Recognition Mechanism of the Cancer and Pathogenic Epitope, LacdiNAc by Immune-Related Lectins
AU - Lima, Carlos D. L.
AU - Coelho, Helena
AU - Gimeno, Ana
AU - Trovão, Filipa
AU - Diniz, Ana
AU - Dias, Jorge S.
AU - Jiménez-Barbero, Jesús
AU - Corzana, Francisco
AU - Carvalho, Ana Luísa
AU - Cabrita, Eurico J.
AU - Marcelo, Filipa
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00780%2F2015%2FCP1293%2FCT0002/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F142847%2F2018/PT#
; PTDC/BIA‐MIB/31028/2017 as well as the PhD grant attributed to A.D. The NMR spectrometers are part of the National NMR Network (PT NMR) and are partially supported by Infrastructure Project No 22161 (co‐financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). A.L.C. and F.T. thank the ALBA synchrotron (Barcelona, Spain) for access to beamline BL13‐XALOC and FCT‐Portugal for project RECI/BBB‐BEP/0124/2012, which financed the Macromolecular Crystallography facilities in UCIBIO. J.J.B. and A.G. acknowledge ERC‐2017‐AdG (788143‐RECGLYCA NMR), Agencia Estatal Investigacion of Spain (RTI2018‐094751‐BC21) and Severo Ochoa Excellence Accreditation (SEV‐2016‐0644). F.C. thanks Agencia Estatal de Investigación (RTI2018‐099592‐B‐C21). F.M. and J.J.B. acknowledge to the European commission for the COST Action 18132‐GLYCONANOPROBES.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/20
Y1 - 2021/5/20
N2 - 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.
AB - 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.
KW - glycan-protein interactions
KW - hGal-3
KW - hMGL
KW - LacdiNAc
KW - molecular recognition
UR - http://www.scopus.com/inward/record.url?scp=85105179578&partnerID=8YFLogxK
U2 - 10.1002/chem.202100800
DO - 10.1002/chem.202100800
M3 - Article
C2 - 33826192
AN - SCOPUS:85105179578
SN - 0947-6539
VL - 27
SP - 7951
EP - 7958
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 29
ER -
