Linking structure and thermal stability of the beta-galactoside-binding protein galectin-1 to ligand binding and dimerization equilibria.

DI LELLA S,; MARTI MA,; CROCI DO,; GUARDIA CM,; DIAZ-RICCI JC,; RABINOVICH GA,; CARAMELO JJ,; ESTRIN DA

BIOCHEMISTRY

AMER CHEMICAL SOC

Año: 2010

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 multifunctional beta-galactoside-binding protein, upon binding to the disaccharide lactose. Analysis of structural changes occurring upon lectin binding to its specific glycans, and thermal denaturation of the protein and the complex were analyzed by circular dichroism. On the other hand, we studied dimerization as another factor that may induce structural and thermal stability changes. The results were then complemented with molecular dynamics simulations and followed by a detailed computation of thermodynamic properties including internal energy, solvation free energy, and conformational entropy. In addition, an energetic profile of the binding and dimerization processes is also presented. Whereas binding and cross-linking of lactose does not alter galectin-1 structure, this interaction leads to substantial changes in the flexibility and internal energy of the protein which confers increased thermal stability to this endogenous lectin. Given that an improved understanding of the physicochemical properties of galectin-glycan lattices may contribute to dissect their biological functions and predict their therapeutic applications, our study suggests that galectin binding to specific disaccharide ligands may increase thermal stability of this glycan-binding protein, an effect which could influence its critical biological functions.