Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output
One of the first and essential steps in gene expression regulation involves the recruitment of transcription factors (TFs) to specific response elements located at enhancers and/or promoters of targeted genes. These DNA elements have a certain variability in both sequence and length, which may affec...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n12_p_Alvarez http://hdl.handle.net/20.500.12110/paper_19326203_v12_n12_p_Alvarez |
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paper:paper_19326203_v12_n12_p_Alvarez2023-06-08T16:30:37Z Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output DNA glucocorticoid receptor transcription factor coordination compound DNA glucocorticoid receptor protein binding zinc amino acid substitution Article dimerization DNA structure molecular dynamics molecular mechanics nonhuman protein DNA binding protein DNA interaction protein domain wild type amino acid sequence animal binding site chemistry conformation genetic transcription hydrogen bond molecular dynamics promoter region protein domain protein multimerization protein quaternary structure rat Amino Acid Sequence Animals Binding Sites Coordination Complexes DNA Hydrogen Bonding Molecular Dynamics Simulation Nucleic Acid Conformation Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Multimerization Protein Structure, Quaternary Rats Receptors, Glucocorticoid Transcription, Genetic Zinc One of the first and essential steps in gene expression regulation involves the recruitment of transcription factors (TFs) to specific response elements located at enhancers and/or promoters of targeted genes. These DNA elements have a certain variability in both sequence and length, which may affect the final transcriptional output. The molecular mechanisms in which TFs integrate the subtle differences within specific recognition sequences to offer different transcriptional responses is still largely unknown. Here we used molecular dynamics simulations to study the DNA binding behavior of the glucocorticoid receptor (GR), a ligand-regulated TF with pleiotropic effects in almost all cells. By comparing the behavior of the wild type receptor and a well characterized Ala477Thr substitution within the rat GR DNA binding domain, we found that the region that connects the two-zinc fingers (i.e. the lever arm) would likely play a key role in GR transcriptional output. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n12_p_Alvarez http://hdl.handle.net/20.500.12110/paper_19326203_v12_n12_p_Alvarez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
DNA glucocorticoid receptor transcription factor coordination compound DNA glucocorticoid receptor protein binding zinc amino acid substitution Article dimerization DNA structure molecular dynamics molecular mechanics nonhuman protein DNA binding protein DNA interaction protein domain wild type amino acid sequence animal binding site chemistry conformation genetic transcription hydrogen bond molecular dynamics promoter region protein domain protein multimerization protein quaternary structure rat Amino Acid Sequence Animals Binding Sites Coordination Complexes DNA Hydrogen Bonding Molecular Dynamics Simulation Nucleic Acid Conformation Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Multimerization Protein Structure, Quaternary Rats Receptors, Glucocorticoid Transcription, Genetic Zinc |
| spellingShingle |
DNA glucocorticoid receptor transcription factor coordination compound DNA glucocorticoid receptor protein binding zinc amino acid substitution Article dimerization DNA structure molecular dynamics molecular mechanics nonhuman protein DNA binding protein DNA interaction protein domain wild type amino acid sequence animal binding site chemistry conformation genetic transcription hydrogen bond molecular dynamics promoter region protein domain protein multimerization protein quaternary structure rat Amino Acid Sequence Animals Binding Sites Coordination Complexes DNA Hydrogen Bonding Molecular Dynamics Simulation Nucleic Acid Conformation Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Multimerization Protein Structure, Quaternary Rats Receptors, Glucocorticoid Transcription, Genetic Zinc Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| topic_facet |
DNA glucocorticoid receptor transcription factor coordination compound DNA glucocorticoid receptor protein binding zinc amino acid substitution Article dimerization DNA structure molecular dynamics molecular mechanics nonhuman protein DNA binding protein DNA interaction protein domain wild type amino acid sequence animal binding site chemistry conformation genetic transcription hydrogen bond molecular dynamics promoter region protein domain protein multimerization protein quaternary structure rat Amino Acid Sequence Animals Binding Sites Coordination Complexes DNA Hydrogen Bonding Molecular Dynamics Simulation Nucleic Acid Conformation Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Multimerization Protein Structure, Quaternary Rats Receptors, Glucocorticoid Transcription, Genetic Zinc |
| description |
One of the first and essential steps in gene expression regulation involves the recruitment of transcription factors (TFs) to specific response elements located at enhancers and/or promoters of targeted genes. These DNA elements have a certain variability in both sequence and length, which may affect the final transcriptional output. The molecular mechanisms in which TFs integrate the subtle differences within specific recognition sequences to offer different transcriptional responses is still largely unknown. Here we used molecular dynamics simulations to study the DNA binding behavior of the glucocorticoid receptor (GR), a ligand-regulated TF with pleiotropic effects in almost all cells. By comparing the behavior of the wild type receptor and a well characterized Ala477Thr substitution within the rat GR DNA binding domain, we found that the region that connects the two-zinc fingers (i.e. the lever arm) would likely play a key role in GR transcriptional output. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. |
| title |
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| title_short |
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| title_full |
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| title_fullStr |
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| title_full_unstemmed |
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| title_sort |
molecular dynamics simulations of the glucocorticoid receptor dna-binding domain suggest a role of the lever-arm mobility in transcriptional output |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n12_p_Alvarez http://hdl.handle.net/20.500.12110/paper_19326203_v12_n12_p_Alvarez |
| _version_ |
1768545245572628480 |