ArticleProceedings of the National Academy of Sciences of the United States of America2015
Designed protein reveals structural determinants of extreme kinetic stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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, 41 citations in OpenAlex.
- Article
- Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity.Frontiers in molecular biosciences · 2023Article
- Spontaneous Orthogonal Protein Crosslinking via a Genetically Encoded 2-Carboxy-4-Aryl-1,2,3-Triazole.Angewandte Chemie (International ed. in English) · 2022Article
- Proteome-wide landscape of solubility limits in a bacterial cell.Scientific reports · 2022Article
- Variable and Conserved Regions of Secondary Structure in the β-Trefoil Fold: Structure Versus Function.Frontiers in molecular biosciences · 2022Article
- Cooperative hydrophobic core interactions in the β-trefoil architecture.Protein science : a publication of the Protein Society · 2021Article
- Conserved buried water molecules enable the β-trefoil architecture.Protein science : a publication of the Protein Society · 2020Article
- An extensively glycosylated archaeal pilus survives extreme conditions.Nature microbiology · 2019Article
- Article
- Kinetic stability of membrane proteins.Biophysical reviews · 2017Review
- Computational tools help improve protein stability but with a solubility tradeoff.The Journal of biological chemistry · 2017Article
- Evidence for the principle of minimal frustration in the evolution of protein folding landscapes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Quality over quantity: optimizing co-translational protein folding with non-'optimal' synonymous codons.Current opinion in structural biology · 2016Review
- How to Build a Complex, Functional Propeller Protein, From Parts.Trends in biochemical sciences · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
The design of stable, functional proteins is difficult. Improved design requires a deeper knowledge of the molecular basis for design outcomes and properties. We previously used a bioinformatics and energy function method to design a symmetric superfold protein composed of repeating structural elements with multivalent carbohydrate-binding function, called ThreeFoil. This and similar methods have produced a notably high yield of stable proteins. Using a battery of experimental and computational analyses we show that despite its small size and lack of disulfide bonds, ThreeFoil has remarkably high kinetic stability and its folding is specifically chaperoned by carbohydrate binding. It is also extremely stable against thermal and chemical denaturation and proteolytic degradation. We demonstrate that the kinetic stability can be predicted and modeled using absolute contact order (ACO) and long-range order (LRO), as well as coarse-grained simulations; the stability arises from a topology that includes many long-range contacts which create a large and highly cooperative energy barrier for unfolding and folding. Extensive data from proteomic screens and other experiments reveal that a high ACO/LRO is a general feature of proteins with strong resistances to denaturation and degradation. These results provide tractable approaches for predicting resistance and designing proteins with sufficient topological complexity and long-range interactions to accommodate destabilizing functional features as well as withstand chemical and proteolytic challenge.
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