Linking the structure and thermal stability of beta-galactoside-binding protein galectin-1 to ligand binding and dimerization equilibria.
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 binding of lectin 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 followed by a detailed computation of thermodynamic properties, including the 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 do 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 the dissection of their biological functions and prediction of their therapeutic applications, our study suggests that galectin binding to specific disaccharide ligands may increase the thermal stability of this glycan-binding protein, an effect that could influence its critical biological functions.
Di Lella
Santiago
S
Departamento de Química Inorgánica, Analítica y Química-Física (INQUIMAE-CONICET), Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
Martí
Marcelo A
MA
Croci
Diego O
DO
Guardia
Carlos M A
CM
Díaz-Ricci
Juan C
JC
Rabinovich
Gabriel A
GA
Caramelo
Julio J
JJ
Estrin
Darío A
DA
D001665:Binding Sites; D019281:Dimerization; D005697:Galactosides / Q000737:chemistry* / Q000378:metabolism*; D037483:Galectin 1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017510:Protein Folding; D013816:Thermodynamics
D005697:Galactosides; D037483:Galectin 1; D008024:Ligands; C007816:beta-galactoside