Institution: | 1. UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal
These authors contribute equally to this work.;2. CIC bioGUNE, Bizkaia, Technology Park, Building 801A, 48170 Derio, Spain;3. UCIBIO, REQUIMTE, Departamento de Quimica, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal;4. CIC bioGUNE, Bizkaia, Technology Park, Building 801A, 48170 Derio, Spain
Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain;5. Departamento de Quimica, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006 Logroño, Spain |
Abstract: | 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. |