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; CARAMELO, JULIO JAVIER; DÍAZ RICCI, JUAN CARLOS; RABINOVICH, GABRIEL ADRIÁN; ESTRIN, DARÍO ARIEL

Salta

Encuentro; XXXIX Annual Meeting of the Argentinean Biophysical Society SAB 2010, workshop CeBEM, structural biology in Latin America, 3rd Latin American Protein Society Meeting; 2010

Sociedad Argentina de Biofísica

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 β-galactoside-binding protein, upon bindingto the disaccharide lactose. Analysis of structural changes occurring upon lectin binding to its specific glycans, and thermal denaturation of the protein and the complex wereanalyzed by circular dichroism. On the other hand, we studied dimerization as anotherfactor that may induce structural and thermal stability changes. The results were thencomplemented with molecular dynamics simulations and followed by a detailed computationof thermodynamic properties including internal energy, solvation free energy, andconformational entropy. In addition, an energetic profile of the binding and dimerizationprocesses is also presented. Whereas binding and cross-linking of lactose does not altergalectin-1 structure, this interaction leads to substantial changes in the flexibility and internalenergy of the protein which confers increased thermal stability to this endogenouslectin.Given that an improved understanding of the physicochemical properties of galectin-glycan lattices may contribute to dissect their biological functions and predict theirtherapeutic applications, our study suggests that galectin binding to specific disaccharideligands may increase thermal stability of this glycan-binding protein, an effect whichcould influence its critical biological functions.