ArticleJournal of molecular biology2011
Folding kinetics of the cooperatively folded subdomain of the IκBα ankyrin repeat domain.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.JACS Au · 2026Article
- Evolution and folding of repeat proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Large Ankyrin repeat proteins are formed with similar and energetically favorable units.PloS one · 2020Article
- PFDB: A standardized protein folding database with temperature correction.Scientific reports · 2019Article
- Folding cooperativity and allosteric function in the tandem-repeat protein class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.Biophysical journal · 2018Article
- Inferring repeat-protein energetics from evolutionary information.PLoS computational biology · 2017Article
- Functional importance of stripping in NFκB signaling revealed by a stripping-impaired IκBα mutant.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Highly polarized C-terminal transition state of the leucine-rich repeat domain of PP32 is governed by local stability.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Direct observation of parallel folding pathways revealed using a symmetric repeat protein system.Biophysical journal · 2014Article
- Diffuse transition state structure for the unfolding of a leucine-rich repeat protein.Physical chemistry chemical physics : PCCP · 2014Article
- Detecting repetitions and periodicities in proteins by tiling the structural space.The journal of physical chemistry. B · 2013Article
- Single-molecule FRET reveals the native-state dynamics of the IκBα ankyrin repeat domain.Journal of molecular biology · 2013Article
- Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα.Journal of molecular biology · 2013Article
- A disorder-induced domino-like destabilization mechanism governs the folding and functional dynamics of the repeat protein IκBα.PLoS computational biology · 2013Article
- Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The ankyrin repeat (AR) domain of IκBα consists of a cooperative folding unit of roughly four ARs (AR1-AR4) and of two weakly folded repeats (AR5 and AR6). The kinetic folding mechanism of the cooperative subdomain, IκBα(67-206), was analyzed using rapid mixing techniques. Despite its apparent architectural simplicity, IκBα(67-206) displays complex folding kinetics, with two sequential on-pathway high-energy intermediates. The effect of mutations to or away from the consensus sequences of ARs on folding behavior was analyzed, particularly the GXTPLHLA motif, which have not been examined in detail previously. Mutations toward the consensus generally resulted in an increase in folding stability, whereas mutations away from the consensus resulted in decreased overall stability. We determined the free energy change upon mutation for three sequential transition state ensembles along the folding route for 16 mutants. We show that folding initiates with the formation of the interface of the outer helices of AR3 and AR4, and then proceeds to consolidate structure in these repeats. Subsequently, AR1 and AR2 fold in a concerted way in a single kinetic step. We show that this mechanism is robust to the presence of AR5 and AR6 as they do not strongly affect the folding kinetics. Overall, the protein appears to fold on a rather smooth energy landscape, where the folding mechanism conforms a one-dimensional approximation. However, we note that the AR does not necessarily act as a single folding element.
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