ArticleProceedings of the National Academy of Sciences of the United States of America2009
Exploring the folding energy landscape of a series of designed consensus tetratricopeptide repeat proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates.Chemical science · 2025Article
- Unraveling the Mechanics of a Repeat-Protein Nanospring: From Folding of Individual Repeats to Fluctuations of the Superhelix.ACS nano · 2022Article
- Engineering mono- and multi-valent inhibitors on a modular scaffold.Chemical science · 2021Article
- Competition of individual domain folding with inter-domain interaction in WW domain engineered repeat proteins.Physical chemistry chemical physics : PCCP · 2019Article
- Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold.Scientific reports · 2019Article
- TPR-containing proteins control protein organization and homeostasis for the endoplasmic reticulum.Critical reviews in biochemistry and molecular biology · 2019Review
- 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
- Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.Journal of molecular biology · 2016Article
- Designed protein reveals structural determinants of extreme kinetic stability.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
- Direct observation of parallel folding pathways revealed using a symmetric repeat protein system.Biophysical journal · 2014Article
- CARPe diem.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
- How well does a funneled energy landscape capture the folding mechanism of spectrin domains?The journal of physical chemistry. B · 2013Article
- LcrH, a class II chaperone from the type three secretion system, has a highly flexible native structure.The Journal of biological chemistry · 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
- Erratum issued
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Repeat proteins contain short, tandem arrays of simple structural motifs (20-40 aa). These stack together to form nonglobular structures that are stabilized by short-range interactions from residues close in primary sequence. Unlike globular proteins, they have few, if any, long-range nonlocal stabilizing interactions. One ubiquitous repeat is the tetratricopeptide motif (TPR), a 34-aa helix-turn-helix motif. In this article we describe the folding kinetics of a series of 7 designed TPR proteins that are assembled from arraying identical designed consensus repeats (CTPRan). These range from the smallest 2-repeat protein to a large 10-repeat protein (approximately 350 aa). In particular, we describe how the energy landscape changes with the addition of repeat units. The data reveal that although the CTPRa proteins have low local frustration, their highly symmetric, modular native structure is reflected in their multistate kinetics of unfolding and folding. Moreover, although the initial folding of all CTPRan proteins involves a nucleus with similar solvent accessibility, their subsequent folding to the native structure depends directly on repeat number. This corresponds to an increasingly complex landscape that culminates in CTPRa10 populating a misfolded, off-pathway intermediate. These results extend our current understanding of the malleable folding pathways of repeat proteins and highlight the consequences of adding identical repeats to the energy landscape.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.