Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure
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, d...
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paper:paper_09596658_v26_n12_p1317_Romero2023-06-08T15:57:06Z Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure Estrin, Dario Ariel 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 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. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v26_n12_p1317_Romero http://hdl.handle.net/20.500.12110/paper_09596658_v26_n12_p1317_Romero |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Estrin, Dario Ariel Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| topic_facet |
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 |
| description |
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. |
| author |
Estrin, Dario Ariel |
| author_facet |
Estrin, Dario Ariel |
| author_sort |
Estrin, Dario Ariel |
| title |
Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| title_short |
Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| title_full |
Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| title_fullStr |
Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| title_full_unstemmed |
Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| title_sort |
impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v26_n12_p1317_Romero http://hdl.handle.net/20.500.12110/paper_09596658_v26_n12_p1317_Romero |
| work_keys_str_mv |
AT estrindarioariel impactofhumangalectin1bindingtosaccharideligandsondimerdissociationkineticsandstructure |
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1768546501015896064 |