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Título: Low resolution structures of the retinoid X receptor DNA-binding and ligand-binding domains revealed by synchrotron x-ray solution scattering
Autor(es): Fischer, Hannes
Dias, Sandra Martha Gomes
Santos, Maria Auxiliadora Morim
Alves, Adriana C.
Zanchin, Nilson
Craievich, Aldo Felix
Apriletti, James W.
Baxter, John Darling
Webb, Paul
Neves, Francisco de Assis Rocha
Ribeiro, Ralff Carvalho Justiniano
Polikarpov, Igor
Assunto: Receptores nucleares
Proteínas - análise
DNA
Data de publicação: Mai-2003
Editora: The American Society for Biochemistry and Molecular Biology
Referência: FISCHER, Hannes et al. Low resolution structures of the retinoid x receptor DNA-binding and ligand-binding domains revealed by synchrotron x-ray solution scattering. The Journal of Biological Chemistry, EUA, v. 278, n. 18, maio 2003. Disponível em: <http://www.jbc.org/content/278/18/16030.full.pdf+html?sid=8173e574-01d4-4ac4-9fca-71f7558f7599>. Acesso em: 20 maio 2013. DOI: 10.1074/jbc.M206953200.
Resumo: Nuclear receptors are ligand-inducible transcription factors that share structurally related DNA-binding (DBD) and ligand-binding (LBD) domains. Biochemical and structural studies have revealed the modular nature of DBD and LBD. Nevertheless, the domains function in concert in vivo. While high-resolution crystal structures of nuclear receptor DBDs and LBDs are available, there are no x-ray structural studies of nuclear receptor proteins containing multiple domains. We report the solution structures of the human retinoid X receptor DBD-LBD (hRXR AB) region. We obtained ab initio shapes of hRXR AB dimer and tetramer to 3.3 and 1.7 nm resolutions, respectively, and established the position and orientation of the DBD and LBD by fitting atomic coordinates of hRXR DBD and LBD. The dimer is U-shaped with DBDs spaced at 2 nm in a head to head orientation forming an angle of about 10° with respect to each other and with an extensive interface area provided by the LBD. The tetramer is a more elongated X-shaped molecule formed by two dimers in head to head arrangement in which the DBDs are extended from the structure and spaced at about 6 nm. The close proximity of DBDs in dimers may facilitate homodimer formation on DNA; however, for the homodimer to bind to a DNA element containing two directly repeated halfsites, one of the DBDs would need to rotate with respect to the other element. By contrast, the separation of DBDs in the tetramers may account for their decreased ability to recognize DNA.
Licença: The Journal of Biological Chemistry - Authors need NOT contact the journal to obtain rights to reuse their own material. They are automatically granted permission to do the following: Reproduce an article for use in the author's courses. (If the author is employed by an academic institution, that institution also may reproduce the article for teaching purposes.). Fonte: http://www.jbc.org/site/misc/Copyright_Permission.xhtml. Acesso em: 20 maio 2013.
DOI: https://dx.doi.org/10.1074/jbc.M206953200
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