| PMID : |
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 (10512722) |
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| titre : |
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How NF-kappaB can be attracted by its cognate DNA. |
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| auteur(s) : |
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Catherine Tisné ( ) 1, Muriel Delepierre1, Brigitte Hartmann () 2 |
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| laboratoire : |
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| résumé : |
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NF-kappaB is involved in the transcriptional regulation of a large number of genes, in particular those of human immunodeficiency virus (HIV). Recently, we used NMR spectroscopy and molecular modelling to study the solution structure of a native duplex related to the HIV-1 kappaB site, together with a mutated duplex for which a three base-pair change abolishes NF-kappaB binding. The native duplex shows unusual dynamics of the four steps surrounding the kappaB site. Here, we explore the intrinsic properties of the NMR-refined structures of both duplexes in order to understand why the native sequence is recognised by NF-kappaB among other DNA sequences. We establish that only the native kappaB site can adopt a conformation where its structure (curvature and base displacement), the accessibility and the electrostatic potentials of key atoms become very favourable for binding the large loops of NF-kappaB, in contrast to the mutated duplex. Finally, we show that the neutralisation of phosphate groups contacted by NF-kappaB favours a more canonical DNA structure. These findings lead to a new hypothesis for specific recognition through the phosphodiester backbone dynamics of the sequences flanking a binding site. Such unusual behaviour confers upon the overall duplex properties that can be used by NF-kappaB to select its binding site. Thus, the selectivity determinants for NF-kappaB binding appear to depend on deformability of an "extended" consensus sequence. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire/Biologie structurale
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0022-2836 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1006/jmbi.1999.3157 |
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| journal : |
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| Journal of Molecular Biology (J Mol Biol) |
| Publisher |
Elsevier |
| ISSN |
0022-2836 (eISSN : 1089-8638) |
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| Audience : |
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internationale |
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| date de publication : |
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15/10/1999 |
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| volume : |
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293 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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139-50 |
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| Descripteur(s) MeSH : |
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Binding Sites – DNA – Genes – Viral – HIV-1 – Magnetic Resonance Spectroscopy – Mutation – NF-kappa B – Nucleic Acid Conformation – Phosphates – Static Electricity |
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