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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Álvarez, L.D., Presman, D.M., Pecci, A.
Formato: JOUR
Materias:
DNA
glucocorticoid receptor
transcription factor
coordination compound
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
promoter region
protein multimerization
protein quaternary structure
rat
Amino Acid Sequence
Animals
Binding Sites
Coordination Complexes
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
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19326203_v12_n12_p_Alvarez
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

Ejemplares similares