Exquisite Binding Mechanism of Human Macrophage GalactoseType Lectin: Insights from the Plasticity of Its Carbohydrate Recognition Domain
Authors: Ana Diniz, Helena Coelho, Jorge S. Dias
DOI: 10.87349/ahuri/170507
Page No: 107-118
Abstract
Human macrophage galactose-type lectin (MGL), expressed on macrophages and dendritic cells (DCs), modulates distinct immune cell responses by recognizing GalNAc-containing structures present on pathogens, self-glycoproteins and tumor cells. Herein, we used NMR spectroscopy and molecular dynamics (MD) simulations to investigate the structural preferences of MGL against different GalNAc-containing structures derived from blood group A antigen, Forssman antigen and the GM2 glycolipid. NMR analyses of the MGL carbohydrate recognition domain (MGL-CRD, C181-H316) in the absence and presence of α-methyl GalNAc, a simple monosaccharide, shows that the MGL-CRD is highly dynamic and its structure is strongly altered upon ligand binding. This plasticity of the MGL-CRD structure explains the ability of MGL to accommodate different GalNAc-containing molecules. However, key differences are observed in the recognition process reliant whether the GalNAc is part of the blood group A antigen, the Forssman antigen or GM2-derived
