ArticleJournal of the American Chemical Society2008
Rerouting the folding pathway of the Notch ankyrin domain by reshaping the energy landscape.
Article in Journal of the American Chemical Society, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- 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
- Unraveling the Mechanics of a Repeat-Protein Nanospring: From Folding of Individual Repeats to Fluctuations of the Superhelix.ACS nano · 2022Article
- Resolving the fine structure in the energy landscapes of repeat proteins.QRB discovery · 2022Article
- Multivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.Frontiers in molecular biosciences · 2022Article
- Protein folding - seeing is deceiving.Protein science : a publication of the Protein Society · 2021Article
- Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold.Scientific reports · 2019Article
- Size and structure of the sequence space of repeat proteins.PLoS computational biology · 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
- Disorder drives cooperative folding in a multidomain protein.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.Journal of molecular biology · 2016Article
- Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- 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
- Single-molecule FRET reveals hidden complexity in a protein energy landscape.Structure (London, England : 1993) · 2015Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
- 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
- Complex energy landscape of a giant repeat protein.Structure (London, England : 1993) · 2013Article
- Insertion of endocellulase catalytic domains into thermostable consensus ankyrin scaffolds: effects on stability and cellulolytic activity.Applied and environmental microbiology · 2013Article
- Take home lessons from studies of related proteins.Current opinion in structural biology · 2013Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The modular nature of repeat proteins has made them a successful target for protein design. Ankyrin repeat, TPR, and leucine rich repeat domains that have been designed solely on consensus information have been shown to have higher thermostability than their biological counterparts. We have previously shown that we can reshape the energy landscape of a repeat protein by adding multiple C-terminal consensus ankyrin repeats to the five N-terminal repeats of the Notch ankyrin domain. Here we explore how the folding mechanism responds to reshaping of the energy landscape. We have used analogous substitutions of a conserved alanine with glycine in each repeat to determine the distribution of structure in the transition state ensembles of constructs containing one (Nank1-5C1) and two consensus (Nank1-5C2) ankyrin repeats. Whereas folding of the wild-type Notch ankyrin domain is slowed by substitutions in its central repeats, (1) folding of Nank1-5C1 and Nank1-5C2 is slowed by substitutions in the C-terminal repeats. Thus, the addition of C-terminal stabilizing repeats shifts the transition state ensemble toward the C-terminal repeats, rerouting the folding pathway of the ankyrin repeat domain. These findings indicate that, for the Notch ankyrin domain, folding pathways are selected based on local energetics.
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