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Consequences of Fuzziness in the NFκB/IκBα Interaction

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Fuzziness

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 725))

Abstract

This chapter provides a short review of various biophysical experiments that have been applied to the inhibitor of kappa B, IκBα and its binding partner, nuclear factor kappa B, or NFκB. The picture that emerges from amide hydrogen/deuterium exchange, NMR and binding kinetics experiments is one in which parts of both proteins are “fuzzy” in the free-state and some parts remain “fuzzy” in the NFκB-IκBα complex. The NFκB family of transcription factors responds to inflammatory cytokines with rapid transcriptional activation, in which NFκB enters the nucleus and binds DNA. Just as rapidly as transcription is activated, it is subsequently repressed by newly synthesized IκBα?that also enters the nucleus and removes NFκB from the DNA. Because IκBα?is an ankyrin repeat protein, it’s “fuzziness” can be controlled by mutagenesis to stabilized the folded state. Experimental comparison with such stabilized mutants helps provide evidence that much of the system control depends on the “fuzziness” of IκBα.

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Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, USA

    Elizabeth A. Komives

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  1. Elizabeth A. Komives
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Editors and Affiliations

  1. Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary

    Monika Fuxreiter PhD

  2. Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary

    Peter Tompa PhD

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© 2012 Landes Bioscience and Springer Science+Business Media

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Komives, E.A. (2012). Consequences of Fuzziness in the NFκB/IκBα Interaction. In: Fuxreiter, M., Tompa, P. (eds) Fuzziness. Advances in Experimental Medicine and Biology, vol 725. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0659-4_5

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