ArticleBiophysical journal2014
Direct observation of parallel folding pathways revealed using a symmetric repeat protein system.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Replacement of the native cis prolines by alanine leads to simplification of the complex folding mechanism of a small globular protein.Biophysical journal · 2023Article
- Stability Islands and the Folding Cooperativity of a Seven-Repeat Array from Topoisomerase V.Journal of the American Chemical Society · 2023Article
- Evolution and folding of repeat proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Functionalization of a symmetric protein scaffold: Redundant folding nuclei and alternative oligomeric folding pathways.Protein science : a publication of the Protein Society · 2022Article
- Unraveling the Mechanics of a Repeat-Protein Nanospring: From Folding of Individual Repeats to Fluctuations of the Superhelix.ACS nano · 2022Article
- Engineering and exploiting synthetic allostery of NanoLuc luciferase.Nature communications · 2022Article
- Multivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.Frontiers in molecular biosciences · 2022Article
- Resolving the fine structure in the energy landscapes of repeat proteins.QRB discovery · 2022Article
- Protein folding - seeing is deceiving.Protein science : a publication of the Protein Society · 2021Article
- Parallel reaction pathways accelerate folding of a guanine quadruplex.Nucleic acids research · 2021Article
- Testing the length limit of loop grafting in a helical repeat protein.Current research in structural biology · 2021Article
- A collection of programs for one-dimensional Ising analysis of linear repeat proteins with point substitutions.Protein science : a publication of the Protein Society · 2021Article
- Large Ankyrin repeat proteins are formed with similar and energetically favorable units.PloS one · 2020Article
- Competition of individual domain folding with inter-domain interaction in WW domain engineered repeat proteins.Physical chemistry chemical physics : PCCP · 2019Article
- Ambidextrous helical nanotubes from self-assembly of designed helical hairpin motifs.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Lessons from pressure denaturation of proteins.Journal of the Royal Society, Interface · 2018Review
- Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Folding cooperativity and allosteric function in the tandem-repeat protein class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Context-Dependent Energetics of Loop Extensions in a Family of Tandem-Repeat Proteins.Biophysical journal · 2018Article
- PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.Biophysical journal · 2018Article
Corrections and comments
- Commented on byCARPe diem.2014
Authors and funding
2 authors.
Funding
Abstract
Although progress has been made to determine the native fold of a polypeptide from its primary structure, the diversity of pathways that connect the unfolded and folded states has not been adequately explored. Theoretical and computational studies predict that proteins fold through parallel pathways on funneled energy landscapes, although experimental detection of pathway diversity has been challenging. Here, we exploit the high translational symmetry and the direct length variation afforded by linear repeat proteins to directly detect folding through parallel pathways. By comparing folding rates of consensus ankyrin repeat proteins (CARPs), we find a clear increase in folding rates with increasing size and repeat number, although the size of the transition states (estimated from denaturant sensitivity) remains unchanged. The increase in folding rate with chain length, as opposed to a decrease expected from typical models for globular proteins, is a clear demonstration of parallel pathways. This conclusion is not dependent on extensive curve-fitting or structural perturbation of protein structure. By globally fitting a simple parallel-Ising pathway model, we have directly measured nucleation and propagation rates in protein folding, and have quantified the fluxes along each path, providing a detailed energy landscape for folding. This finding of parallel pathways differs from results from kinetic studies of repeat-proteins composed of sequence-variable repeats, where modest repeat-to-repeat energy variation coalesces folding into a single, dominant channel. Thus, for globular proteins, which have much higher variation in local structure and topology, parallel pathways are expected to be the exception rather than the rule.
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