INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
UNRAVELING KEY FEATURES OF THE BETA-GALACTOSIDE BINDING PROTEIN GALECTIN-1 IN INTERPLAY WITH LIGAND BINDING AND DIMERIZATION EQUILIBRIA
Autor/es:
DI LELLA, SANTIAGO; CARAMELO, JULIO JAVIER; GUARDIA, CARLOS MANUEL ALBERTO; MARTÍ, MARCELO ADRIÁN; RABINOVICH, GABRIEL ADRIÁN; ESTRIN, DARÍO ARIEL
Lugar:
Baltimore, Maryland
Reunión:
Encuentro; 55th Annual Meeting of the Biophysical Society; 2011
Institución organizadora:
Biophysical Society
Resumen:
Galectin-1 is a multifunctional β-galactoside-binding protein associated with critical biological processes such regulation of immune responses and cellular differentiation. Upon binding to the disaccharide lactose, a model study ligand, subtle changes may be responsible of modulating its function. In this work, structural changes occurring upon binding of galectin-1 to its specific glycans and under different experimental conditions are tested by experimental (i.e. circular dichroism and fluorescence spectroscopy) tools. On the other hand, we studied dimerization as another factor that may induce structural changes. The results are 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, under different conditions. Whereas binding and cross-linking of lactose only subtly alter galectin-1 structure, the interactions lead to substantial changes in the flexibility and internal energy of the protein which confer new properties to this endogenous lectin. Furthermore, key features determining ligand binding at different experimental conditions are analyzed. Provided these physicochemical properties of galectin-glycan interactions, a discussion will be presented on possible biological connotations and prediction of their potential therapeutic applications.
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