title: Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
abstract: Upon viral infection, NF-kappaB translocates to the nucleus and activates the IFN-beta gene by binding to the PRDII element. Strikingly, NF-kappaB loses its ability to activate the IFN-beta gene when the PRDII element is substituted by closely related sites. We report here the crystal structure of NF-kappaB p50/p65 heterodimer bound to the PRDII element from the IFN-beta promoter. The structure reveals an unexpected alteration in configuration, in which the p50 specificity domain moves by as much as approximately 9 A when compared to NF-kappaB heterodimer bound to the immunoglobulin kappaB site (Ig-kappaB) while maintaining the same base-specific contacts with the DNA. Taken together, the structure offers new insights into the allosteric effects of closely related DNA sites on the configuration of NF-kappaB and its transcriptional selectivity.
authors: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Carlos R
authors: CR
authors: Escalante
authors: Leyi
authors: L
authors: Shen
authors: Dimitris
authors: D
authors: Thanos
authors: Aneel K
authors: AK
authors: Aggarwal
mesh_terms: D003460:Crystallization; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D016328:NF-kappa B / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021122:Protein Subunits
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D021122:Protein Subunits; D016899:Interferon-beta; D004247:DNA