ArticleProceedings of the National Academy of Sciences of the United States of America2018
Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Walking the tightrope: Balancing opposing cooperativities in dynein assembly.The Journal of biological chemistry · 2026Article
- Stability and cooperativity in chimeric de novo TIM barrels via quarter swapping.Protein science : a publication of the Protein Society · 2026Article
- Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity.Frontiers in molecular biosciences · 2023Article
- Unraveling the Mechanics of a Repeat-Protein Nanospring: From Folding of Individual Repeats to Fluctuations of the Superhelix.ACS nano · 2022Article
- Surface residues and nonadditive interactions stabilize a consensus homeodomain protein.Biophysical journal · 2021Article
- Analysis of Tandem Repeat Protein Folding Using Nearest-Neighbor Models.Annual review of biophysics · 2021Review
- Design of multi-scale protein complexes by hierarchical building block fusion.Nature communications · 2021Article
- The Effect of Mutations in the TPR and Ankyrin Families of Alpha Solenoid Repeat Proteins.Frontiers in bioinformatics · 2021Review
- Practically useful protein-design methods combining phylogenetic and atomistic calculations.Current opinion in structural biology · 2020Review
- Modular repeat protein sculpting using rigid helical junctions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Information theoretic measures for quantifying sequence-ensemble relationships of intrinsically disordered proteins.Protein engineering, design & selection : PEDS · 2019Article
- Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold.Scientific reports · 2019Article
- Role of antibody heavy and light chain interface residues in affinity maturation of binding to HIV envelope glycoprotein.Molecular systems design & engineering · 2019Article
- Functional instability allows access to DNA in longer transcription Activator-Like effector (TALE) arrays.eLife · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Designed helical repeats (DHRs) are modular helix-loop-helix-loop protein structures that are tandemly repeated to form a superhelical array. Structures combining tandem DHRs demonstrate a wide range of molecular geometries, many of which are not observed in nature. Understanding cooperativity of DHR proteins provides insight into the molecular origins of Rosetta-based protein design hyperstability and facilitates comparison of energy distributions in artificial and naturally occurring protein folds. Here, we use a nearest-neighbor Ising model to quantify the intrinsic and interfacial free energies of four different DHRs. We measure the folding free energies of constructs with varying numbers of internal and terminal capping repeats for four different DHR folds, using guanidine-HCl and glycerol as destabilizing and solubilizing cosolvents. One-dimensional Ising analysis of these series reveals that, although interrepeat coupling energies are within the range seen for naturally occurring repeat proteins, the individual repeats of DHR proteins are intrinsically stable. This favorable intrinsic stability, which has not been observed for naturally occurring repeat proteins, adds to stabilizing interfaces, resulting in extraordinarily high stability. Stable repeats also impart a downhill shape to the energy landscape for DHR folding. These intrinsic stability differences suggest that part of the success of Rosetta-based design results from capturing favorable local interactions.
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