Structural basis of redox-dependent modulation of galectin-1 dynamics and function
Galectin-1 (Gal-1), a member of a family of multifunctional lectins, plays key roles in diverse biological processes including cell signaling, immunomodulation, neuroprotection and angiogenesis. The presence of an unusual number of six cysteine residues within Gal-1 sequence prompted a detailed anal...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v24_n5_p428_Guardia http://hdl.handle.net/20.500.12110/paper_09596658_v24_n5_p428_Guardia |
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paper:paper_09596658_v24_n5_p428_Guardia2023-06-08T15:57:05Z Structural basis of redox-dependent modulation of galectin-1 dynamics and function circular dichroism cysteine galectin-1 molecular dynamics oxidation arginine carbohydrate carbohydrate recognition domain cysteine galectin 1 glutamic acid hydrogen peroxide lactose polymer unclassified drug galectin 1 LGALS1 protein, human amino acid sequence article binding affinity cell viability circular dichroism conformational transition controlled study disulfide bond human in vitro study molecular dynamics nonhuman oxidation pH priority journal protein expression protein function protein interaction protein structure regulatory mechanism structure activity relation T lymphocyte chemistry metabolism molecular dynamics oxidation reduction reaction protein tertiary structure Galectin 1 Humans Hydrogen Peroxide Molecular Dynamics Simulation Oxidation-Reduction Protein Structure, Tertiary Galectin-1 (Gal-1), a member of a family of multifunctional lectins, plays key roles in diverse biological processes including cell signaling, immunomodulation, neuroprotection and angiogenesis. The presence of an unusual number of six cysteine residues within Gal-1 sequence prompted a detailed analysis of the impact of the redox environment on the functional activity of this lectin. We examined the role of each cysteine residue in the structure and function of Gal-1 using both experimental and computational approaches. Our results show that: (i) only three cysteine residues present in each carbohydrate recognition domain (CRD) (Cys2, Cys16 and Cys88) were important in protein oxidation, (ii) oxidation promoted the formation of the Cys16-Cys88 disulfide bond, as well as multimers through Cys2, (iii) the oxidized protein did not bind to lactose, probably due to poor interactions with Arg48 and Glu71, (iv) in vitro oxidation by air was completely reversible and (v) oxidation by hydrogen peroxide was relatively slow (1.7 ± 0.2 M-1 s-1 at pH 7.4 and 25°C). Finally, an analysis of key cysteines in other human galectins is also provided in order to predict their behaviour in response to redox variations. Collectively, our data provide new insights into the structural basis of Gal-1 redox regulation with critical implications in physiology and pathology. © The Author 2014. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v24_n5_p428_Guardia http://hdl.handle.net/20.500.12110/paper_09596658_v24_n5_p428_Guardia |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
circular dichroism cysteine galectin-1 molecular dynamics oxidation arginine carbohydrate carbohydrate recognition domain cysteine galectin 1 glutamic acid hydrogen peroxide lactose polymer unclassified drug galectin 1 LGALS1 protein, human amino acid sequence article binding affinity cell viability circular dichroism conformational transition controlled study disulfide bond human in vitro study molecular dynamics nonhuman oxidation pH priority journal protein expression protein function protein interaction protein structure regulatory mechanism structure activity relation T lymphocyte chemistry metabolism molecular dynamics oxidation reduction reaction protein tertiary structure Galectin 1 Humans Hydrogen Peroxide Molecular Dynamics Simulation Oxidation-Reduction Protein Structure, Tertiary |
| spellingShingle |
circular dichroism cysteine galectin-1 molecular dynamics oxidation arginine carbohydrate carbohydrate recognition domain cysteine galectin 1 glutamic acid hydrogen peroxide lactose polymer unclassified drug galectin 1 LGALS1 protein, human amino acid sequence article binding affinity cell viability circular dichroism conformational transition controlled study disulfide bond human in vitro study molecular dynamics nonhuman oxidation pH priority journal protein expression protein function protein interaction protein structure regulatory mechanism structure activity relation T lymphocyte chemistry metabolism molecular dynamics oxidation reduction reaction protein tertiary structure Galectin 1 Humans Hydrogen Peroxide Molecular Dynamics Simulation Oxidation-Reduction Protein Structure, Tertiary Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| topic_facet |
circular dichroism cysteine galectin-1 molecular dynamics oxidation arginine carbohydrate carbohydrate recognition domain cysteine galectin 1 glutamic acid hydrogen peroxide lactose polymer unclassified drug galectin 1 LGALS1 protein, human amino acid sequence article binding affinity cell viability circular dichroism conformational transition controlled study disulfide bond human in vitro study molecular dynamics nonhuman oxidation pH priority journal protein expression protein function protein interaction protein structure regulatory mechanism structure activity relation T lymphocyte chemistry metabolism molecular dynamics oxidation reduction reaction protein tertiary structure Galectin 1 Humans Hydrogen Peroxide Molecular Dynamics Simulation Oxidation-Reduction Protein Structure, Tertiary |
| description |
Galectin-1 (Gal-1), a member of a family of multifunctional lectins, plays key roles in diverse biological processes including cell signaling, immunomodulation, neuroprotection and angiogenesis. The presence of an unusual number of six cysteine residues within Gal-1 sequence prompted a detailed analysis of the impact of the redox environment on the functional activity of this lectin. We examined the role of each cysteine residue in the structure and function of Gal-1 using both experimental and computational approaches. Our results show that: (i) only three cysteine residues present in each carbohydrate recognition domain (CRD) (Cys2, Cys16 and Cys88) were important in protein oxidation, (ii) oxidation promoted the formation of the Cys16-Cys88 disulfide bond, as well as multimers through Cys2, (iii) the oxidized protein did not bind to lactose, probably due to poor interactions with Arg48 and Glu71, (iv) in vitro oxidation by air was completely reversible and (v) oxidation by hydrogen peroxide was relatively slow (1.7 ± 0.2 M-1 s-1 at pH 7.4 and 25°C). Finally, an analysis of key cysteines in other human galectins is also provided in order to predict their behaviour in response to redox variations. Collectively, our data provide new insights into the structural basis of Gal-1 redox regulation with critical implications in physiology and pathology. © The Author 2014. |
| title |
Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| title_short |
Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| title_full |
Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| title_fullStr |
Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| title_full_unstemmed |
Structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| title_sort |
structural basis of redox-dependent modulation of galectin-1 dynamics and function |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v24_n5_p428_Guardia http://hdl.handle.net/20.500.12110/paper_09596658_v24_n5_p428_Guardia |
| _version_ |
1768542747076067328 |