title: Structural characterization of the ternary complex that mediates termination of NF-κB signaling by IκBα.
abstract: The transcription factor NF-κB is used in many systems for the transduction of extracellular signals into the expression of signal-responsive genes. Published structural data explain the activation of NF-κB through degradation of its dedicated inhibitor IκBα, but the mechanism by which NF-κB-mediated signaling is turned off by its removal from the DNA in the presence of newly synthesized IκBα (termed stripping) is unknown. Previous kinetic studies showed that IκBα accelerates NF-κB dissociation from DNA, and a transient ternary complex between NF-κB, its cognate DNA sequence, and IκBα was observed. Here we structurally characterize the >100-kDa ternary complex by NMR and negative stain EM and show a modeled structure that is consistent with the measurements. These data provide a structural basis for previously unidentified insights into the molecular mechanism of stripping.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037-1000;
authors.forename: Sulakshana P
authors.initials: SP
authors.lastname: Mukherjee
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037-1000;
authors.forename: Pedro O
authors.initials: PO
authors.lastname: Quintas
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037-1000;
authors.forename: Reginald
authors.initials: R
authors.lastname: McNulty
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92037-0378.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Komives
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037-1000; dyson@scripps.edu.
authors.forename: H Jane
authors.identifier: 0000-0001-6855-3398
authors.initials: HJ
authors.lastname: Dyson
mesh_terms: D004247:DNA / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D000072000:NF-KappaB Inhibitor alpha / Q000737:chemistry*; D016328:NF-kappa B / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA
keywords: NMR; negative stain electron microscopy; protein–DNA complex; protein–protein complex; transcriptional activation