Visualization of the nanospring dynamics of the IκBα ankyrin repeat domain in real time

Jorge A. Lamboy, Hajin Kim, Kyung Suk Lee, Taekjip Ha, Elizabeth A. Komives

Research output: Contribution to journalArticle

Abstract

IκBα is a crucial regulator of NFκB transcription. NFκB-mediated gene activation is robust because levels of free IκBα are kept extremely low by rapid, ubiquitin-independent degradation of newly synthesized IκBα. IκBα has a weakly folded ankyrin repeat 5-6 (AR5-6) region that is critical in establishing its short intracellular half-life. The AR5-6 region of IκBα folds upon binding to NFκB. The NFκB-bound IκBα has a long half-life and requires ubiquitin-targeted degradation. We present single molecule FRET evidence that the native state of IκBα transiently populates an intrinsically disordered state characterized by a more extended structure and fluctuations on the millisecond time scale. Binding to NFκB or introduction of stabilizing mutations in AR 6 suppressed the fluctuations, whereas higher temperature or small amounts of urea increased them. The results reveal that intrinsically disordered protein regions transition between collapsed and extended conformations under native conditions.

Original languageEnglish (US)
Pages (from-to)10178-10183
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number25
DOIs
StatePublished - Jun 21 2011

Keywords

  • Intrinsically disordered protein
  • NFkappaB
  • Protein dynamics
  • Transcription factor

ASJC Scopus subject areas

  • General

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