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Adv Exp Med Biol. 2012;725:74-85. doi: 10.1007/978-1-4614-0659-4_5.

Consequences of fuzziness in the NFκB/IκBα interaction.

Author information

1
Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, USA. ekomives@ucsd.edu

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.

PMID:
22399319
PMCID:
PMC3603378
DOI:
10.1007/978-1-4614-0659-4_5
[Indexed for MEDLINE]
Free PMC Article

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