Structural​ and biochemical​ ​features of Galectin​s governing ​their biological activity

RABINOVICH, GABRIEL ADRIÁN; DI LELLA, SANTIAGO

Mandelieu la Napoule

Workshop; Transducing glycan information into function: Lessons from galectins; 2016

EMBO

In the past decade,​significant efforts have been ​made to delineate the intracellular and extracellular functions of galectins​, multifunctional ​proteins capable of monitoring​ glycan​ changes occurring onthe cell surface during fundamental biological processes. Theirwidely conserved structures, exquisite​, although in some cases promiscuous​ carbohydrate specificity , and ​their ability to modulate avariety of biological processes have captivated a broad range ofscientists from different disciplines.However, despite​ considerable efforts in dissecting the functions and properties of theseglycan-binding proteins, we still lack a comprehensive ​understanding onhow structural and biochemical aspects of these proteins can  influence biological functions.Gal-1,a proto-type member of the galectinfamily displaysat a glance a structure thatappears to be quite simple, although afew peculiarities make it highlyversatile. Firstly,even thought its binding domain is amonomer, a subtle homodimerizationequilibrium at physiologic concentrations modulatesits function in a particular way.The complex kinetic and thermodynamicequilibriacritically govern the function​ and signaling​ of this lectin  by allowinginteractions with a preferential set of glycosylated receptors. Onanother hand, the presence of some key amino acid, such as anunusual number of cysteine residues or a few environmental sensorresidues, appears to govern key ​properties of Gal-1 functionalactivity. We will presentstructural and chemical determinants of Gal-1 that in a precise and subtle mannerappear to modulate its biological function, with the use of combinedexperimental and computational approaches. We aim to integratestructural, biochemical, and functional aspects of this criticalcarbohydrate binding protein and discuss their implications indiverse physiologic and pathologic settings​ with the ultimate goal of designing potential galectin and glycan-based therapeutic agents.