Visualization of the nanospring dynamics of the IkappaBalpha ankyrin repeat domain in real time.

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 h

SUBMITTER: Lamboy JA 

PROVIDER: S-EPMC3121830 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature