INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
artículos
Título:
Linking structure and thermal stability of the β-galactoside-binding protein galectin-1 to ligand binding and dimerization equilibria.
Autor/es:
SANTIAGO DI LELLA; MARCELO A. MARTI; DIEGO O CROCI; CARLOS A GUARDIA; JUAN C. D. RICCI; GABRIEL A. RABINOVICH; JULIO J CARAMELO; DARIO A ESTRIN
Revista:
BIOCHEMISTRY
Editorial:
AMER CHEMICAL SOC
Referencias:
Año: 2010 p. 7652 - 7658
ISSN:
0006-2960
Resumen:
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.