Comparative study of binding abilities of Siglec-7 to different ligands using molecular modeling techniques and structural analysis

Abstract

Sialic acid binding Ig-like lectins (siglecs) are type I membrane proteins characterized by their sequence similarity and ability to bind sialic acid moieties in glycoproteins and glycolipids. Siglecs can regulate the functions of cells in the innate and adaptive immune systems and promote cell–cell interactions through glycan recognition. Siglec-7, a member of the siglec family, is expressed on NK cells and displays unique ligand binding properties different from the other member of the Siglec family. Siglec-7 prefers α(2,8)-disialyl group and branched α(2,6)-sialyl group containing ligands. In this paper, complexes of Siglec-7 in solution with α(2,8)-disialyl group containing ligand GD3, branched α(2,6)-sialyl group containing ligand LSTb and α(2,6)-sialyl group containing ligand LSTc have been modeled based on the crystal structure of Siglec7-DSLc4[α(2,3)/α(2,6)-disialyl lactotetraosyl 2-(trimethylsilyl)ethyl] complex. Structural analysis of these complexes and calculation of theoretical dissociation constant values helped to conclude that GD3 and LSTb can form better complex with Siglec7 than LSTc in solution and all the ligands, DSLc4, GD3, LSTb, and LSTc can form better complexes in solution than in the crystal structure.