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Abstract:

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.

Registro:

Documento: Artículo
Título:Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output
Autor:Álvarez, L.D.; Presman, D.M.; Pecci, A.
Filiación:Universidad de Buenos Aires, CONICET, UMYMFOR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Building 41, 41 Library Drive, Bethesda, MD, United States
Universidad de Buenos Aires, CONICET, IFIBYNE, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Palabras clave: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
Año:2017
Volumen:12
Número:12
DOI: http://dx.doi.org/10.1371/journal.pone.0189588
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:DNA, 9007-49-2; zinc, 7440-66-6, 14378-32-6; Coordination Complexes; DNA; Receptors, Glucocorticoid; Zinc
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n12_p_Alvarez

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Citas:

---------- APA ----------
Álvarez, L.D., Presman, D.M. & Pecci, A. (2017) . Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output. PLoS ONE, 12(12).
http://dx.doi.org/10.1371/journal.pone.0189588
---------- CHICAGO ----------
Álvarez, L.D., Presman, D.M., Pecci, A. "Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output" . PLoS ONE 12, no. 12 (2017).
http://dx.doi.org/10.1371/journal.pone.0189588
---------- MLA ----------
Álvarez, L.D., Presman, D.M., Pecci, A. "Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output" . PLoS ONE, vol. 12, no. 12, 2017.
http://dx.doi.org/10.1371/journal.pone.0189588
---------- VANCOUVER ----------
Álvarez, L.D., Presman, D.M., Pecci, A. Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output. PLoS ONE. 2017;12(12).
http://dx.doi.org/10.1371/journal.pone.0189588