Lactose Binding To Galectin-1 Occurs With Negative Cooperativity and Attenuates Internal Motions Throughout the Protein

Abstract

Galectins are a sub-family of lectins with a conserved carbohydrate recognition domain (CRD) that interacts with beta-galactosides. By binding cell surface glycoconjugates, galectin-1 is involved in cell adhesion and migration processes and is an important regulator of tumor angiogenesis. Here, we used heteronuclear NMR spectroscopy and molecular modeling to investigate lactose binding to galectin-1 and to derive solution NMR structures of galectin-1 in the lactose bound and unbound states. Structure analysis shows that the beta-strands and loops around the lactose binding site which are more open and dynamic in the unbound state, fold in around the bound lactose molecule dampening internal motions at that site. Analysis of titration binding data reveal that lactose binds the two CRDs of the galectin-1 dimer with negative cooperativity. Molecular dynamics simulations provide insight into structural dynamics of the half-loaded lactose state and, together with NMR data, suggest that lactose binding at one site transmits a signal through the beta-sandwich and loops to the second binding site. Overall, our results provide new insight into galectin-1 structure-function relationships and to protein-carbohydrate interactions in general.