Abstract:
Endogenous lectins can control critical biological responses, including cell communication, signaling, angiogenesis and immunity by decoding glycan-containing information on a variety of cellular receptors and the extracellular matrix. Galectin-1 (Gal-1), a prototype member of the galectin family, displays only one carbohydrate recognition domain and occurs in a subtle homodimerization equilibrium at physiologic concentrations. Such equilibrium critically governs the function of this lectin signaling by allowing tunable interactions with a preferential set of glycosylated receptors. Here, we used a combination of experimental and computational approaches to analyze the kinetics and mechanisms connecting Gal-1 ligand unbinding and dimer dissociation processes. Kinetic constants of both processes were found to differ by an order of magnitude. By means of steered molecular dynamics simulations, the ligand unbinding process was followed monitoring water occupancy changes. By determining the water sites in a carbohydrate binding place during the unbinding process, we found that rupture of ligand-protein interactions induces an increase in energy barrier while ligand unbinding process takes place, whereas the entry of water molecules to the binding groove and further occupation of their corresponding water sites contributes to lowering of the energy barrier. Moreover, our findings suggested local asymmetries between the two subunits in the dimer structure detected at a nanosecond timescale. Thus, integration of experimental and computational data allowed a more complete understanding of lectin ligand binding and dimerization processes, suggesting new insights into the relationship between Gal-1 structure and function and renewing the discussion on the biophysics and biochemistry of lectin-ligand lattices. © The Author 2016.
Registro:
Documento: |
Artículo
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Título: | Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
Autor: | Romero, J.M.; Trujillo, M.; Estrin, D.A.; Rabinovich, G.A.; Di Lella, S. |
Filiación: | Departamento de Química Biológica, IQUIBICEN, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina Departamento de Química Inorgánica, Analítica y Química Física, INQUIMAE, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina Departamento de Bioquímica, Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, 11800, Uruguay Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, CONICET, Ciudad de Buenos Aires, C1428ADN, Argentina Institute of Biology, Humboldt-Universität zu Berlin, Invalidenstraße 43, Berlin, 10115, Germany
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Palabras clave: | Carbohydrate-binding protein; Dimer dissociation kinetics; Galectin-1; Lattices; Ligand-binding kinetics; carbohydrate; dimer; galectin 1; lactose; lectin; ligand; monomer; water; galectin 1; LGALS1 protein, human; polysaccharide; Article; beta sheet; dilution; dimerization; dissociation; dissociation constant; energy; enthalpy; entropy; equilibrium constant; fluorescence spectroscopy; human; hydrogen bond; kinetics; ligand binding; ligand protein interaction; molecular dynamics; molecular mechanics; nonhuman; priority journal; protein interaction; proton transport; quantum mechanics; static electricity; surface area; binding site; chemistry; kinetics; metabolism; protein conformation; thermodynamics; Binding Sites; Dimerization; Galectin 1; Humans; Kinetics; Ligands; Molecular Dynamics Simulation; Polysaccharides; Protein Conformation; Thermodynamics |
Año: | 2016
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Volumen: | 26
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Número: | 12
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Página de inicio: | 1317
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Página de fin: | 1327
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DOI: |
http://dx.doi.org/10.1093/glycob/cww052 |
Título revista: | Glycobiology
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Título revista abreviado: | Glycobiology
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ISSN: | 09596658
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CODEN: | GLYCE
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CAS: | galectin 1, 258495-34-0; lactose, 10039-26-6, 16984-38-6, 63-42-3, 64044-51-5; water, 7732-18-5; Galectin 1; LGALS1 protein, human; Ligands; Polysaccharides
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v26_n12_p1317_Romero |
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Citas:
---------- APA ----------
Romero, J.M., Trujillo, M., Estrin, D.A., Rabinovich, G.A. & Di Lella, S.
(2016)
. Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure. Glycobiology, 26(12), 1317-1327.
http://dx.doi.org/10.1093/glycob/cww052---------- CHICAGO ----------
Romero, J.M., Trujillo, M., Estrin, D.A., Rabinovich, G.A., Di Lella, S.
"Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure"
. Glycobiology 26, no. 12
(2016) : 1317-1327.
http://dx.doi.org/10.1093/glycob/cww052---------- MLA ----------
Romero, J.M., Trujillo, M., Estrin, D.A., Rabinovich, G.A., Di Lella, S.
"Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure"
. Glycobiology, vol. 26, no. 12, 2016, pp. 1317-1327.
http://dx.doi.org/10.1093/glycob/cww052---------- VANCOUVER ----------
Romero, J.M., Trujillo, M., Estrin, D.A., Rabinovich, G.A., Di Lella, S. Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure. Glycobiology. 2016;26(12):1317-1327.
http://dx.doi.org/10.1093/glycob/cww052