ArticlePloS one2013
Understanding the folding-function tradeoff in proteins.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- How soluble misfolded proteins bypass chaperones at the molecular level.Nature communications · 2023Pooled it
- Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics.Science advances · 2025Article
- Heterogeneous folding landscapes and predetermined breaking points within a protein family.Protein science : a publication of the Protein Society · 2024Article
- A review of visualisations of protein fold networks and their relationship with sequence and function.Biological reviews of the Cambridge Philosophical Society · 2023Review
- Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity.Frontiers in molecular biosciences · 2023Article
- Characterization of a Novel Mannose Isomerase from Stenotrophomonas rhizophila and Identification of Its Possible Catalytic Residues.Molecular biotechnology · 2022Article
- Functionalization of a symmetric protein scaffold: Redundant folding nuclei and alternative oligomeric folding pathways.Protein science : a publication of the Protein Society · 2022Article
- A Method for Assessing the Robustness of Protein Structures by Randomizing Packing Interactions.Frontiers in molecular biosciences · 2022Article
- Cooperative hydrophobic core interactions in the β-trefoil architecture.Protein science : a publication of the Protein Society · 2021Article
- How cooperative are protein folding and unfolding transitions?Protein science : a publication of the Protein Society · 2016Review
- Designed protein reveals structural determinants of extreme kinetic stability.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Protein unfolding rates correlate as strongly as folding rates with native structure.Protein science : a publication of the Protein Society · 2015Article
- Geometrical Frustration in Interleukin-33 Decouples the Dynamics of the Functional Element from the Folding Transition State Ensemble.PloS one · 2015Article
- In the multi-domain protein adenylate kinase, domain insertion facilitates cooperative folding while accommodating function at domain interfaces.PLoS computational biology · 2014Article
- Comparing protein folding in vitro and in vivo: foldability meets the fitness challenge.Current opinion in structural biology · 2014Review
- Altered backbone and side-chain interactions result in route heterogeneity during the folding of interleukin-1β (IL-1β).Biophysical journal · 2013Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the "function-less" folding-motif of a protein fold from a set of structurally similar but functionally diverse proteins. We then obtain the β-trefoil folding-motif, and study its folding using structure-based models and molecular dynamics simulations. CompariA protein sequence serves two purpson with the folding of wild-type β-trefoil proteins shows that function affects folding in two ways: In the slower folding interleukin-1β, binding sites make the fold more complex, increase contact order and slow folding. In the faster folding hisactophilin, residues which could have been part of the folding-motif are used for function. This reduces the density of native contacts in functional regions and increases folding rate. The folding-motif helps identify subtle structural deviations which perturb folding. These may then be used for functional annotation. Further, the folding-motif could potentially be used as a first step in the sequence design of function-less scaffold proteins. Desired function can then be engineered into these scaffolds.
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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.