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

Citation data:

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490, Vol: 108, Issue: 25, Page: 10178-83

Publication Year:
2011
Usage 40
Abstract Views 40
Captures 3
Readers 2
Exports-Saves 1
Citations 30
Citation Indexes 30
Repository URL:
http://scholarworks.unist.ac.kr/handle/201301/7107
PMID:
21628581
DOI:
10.1073/pnas.1102226108
PMCID:
PMC3121830
Author(s):
Lamboy, Jorge A.; Kim, Hajin; Lee, Kyung Suk; Ha, Taekjip; Komives, Elizabeth A.
Publisher(s):
Proceedings of the National Academy of Sciences; NATL ACAD SCIENCES
Tags:
Multidisciplinary; Intrinsically disordered protein; NFkappaB; Protein dynamics; Transcription factor
article description
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.