Linking the Structure and Thermal Stability of β-Galactoside-Binding Protein Galectin-1 to Ligand Binding and Dimerization Equilibria

DI LELLA, SANTIAGO; MARTÍ, MARCELO ADRIÁN; CROCI, DIEGO OMAR; GUARDIA, CARLOS MANUEL ALBERTO; DÍAZ RICCI, JUAN CARLOS; RABINOVICH, GABRIEL ADRIÁN; CARAMELO, JULIO JAVIER; ESTRIN, DARÍO ARIEL

BIOCHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington, D. C.; Año: 2010 vol. 49 p. 7652 - 7658

0006-2960

The stability of proteins involves a critical balance of interactions of different orders of magnitude.In this work, we present experimental evidence of an increased thermal stability of galectin-1, a multi-functional β-galactoside-binding protein, upon binding to the disaccharide lactose. Analysis of structuralchanges occurring upon binding of lectin to its specific glycans and thermal denaturation of the protein andthe complex were analyzed by circular dichroism. On the other hand, we studied dimerization as anotherfactor that may induce structural and thermal stability changes. The results were then complemented withmolecular dynamics simulations followed by a detailed computation of thermodynamic properties, includingthe internal energy, solvation free energy, and conformational entropy. In addition, an energetic profile of thebinding and dimerization processes is also presented. Whereas binding and cross-linking of lactose do notalter galectin-1 structure, this interaction leads to substantial changes in the flexibility and internal energy ofthe protein which confers increased thermal stability to this endogenous lectin. Given that an improvedunderstanding of the physicochemical properties of galectin-glycan lattices may contribute to the dissectionof their biological functions and prediction of their therapeutic applications, our study suggests that galectinbinding to specific disaccharide ligands may increase the thermal stability of this glycan-binding protein, aneffect that could influence its critical biological functions.