ArticleProceedings of the National Academy of Sciences of the United States of America2008
Extracting function from a beta-trefoil folding motif.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. 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 49 papers, 1 of them a synthesis that pooled it.
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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- How soluble misfolded proteins bypass chaperones at the molecular level.Nature communications · 2023Pooled it
- Article
- Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics.Science advances · 2025Article
- Diversity and features of proteins with structural repeats.Biophysical reviews · 2023Review
- Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity.Frontiers in molecular biosciences · 2023Article
- Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains.Biophysical journal · 2022Article
- Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases fromInternational journal of molecular sciences · 2022Article
- Investigating the Conformational Dynamics of a Y-Family DNA Polymerase during Its Folding and Binding to DNA and a Nucleotide.JACS Au · 2022Article
- A Method for Assessing the Robustness of Protein Structures by Randomizing Packing Interactions.Frontiers in molecular biosciences · 2022Article
- Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase.eLife · 2020Article
- Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations.Biophysical journal · 2018Article
- Size and topology modulate the effects of frustration in protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- On the folding of a structurally complex protein to its metastable active state.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Folding nucleus structure persists in thermally-aggregated FGF-1.Protein science : a publication of the Protein Society · 2018Article
- Frustration, function and folding.Current opinion in structural biology · 2018Review
- Evolution of a protein folding nucleus.Protein science : a publication of the Protein Society · 2016Article
- MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery.International journal of molecular sciences · 2015Review
- Conformational frustration in calmodulin-target recognition.Journal of molecular recognition : JMR · 2015Article
- Modulation of folding energy landscape by charge-charge interactions: linking experiments with computational modeling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Despite having remarkably similar three-dimensional structures and stabilities, IL-1beta promotes signaling, whereas IL-1Ra inhibits it. Their energy landscapes are similar and have coevolved to facilitate competitive binding to the IL-1 receptor. Nevertheless, we find that IL-1Ra folds faster than IL-1beta. A structural alignment of the proteins shows differences mainly in two loops, a beta-bulge of IL-1beta and a loop in IL-1Ra that interacts with residue K145 and connects beta-strands 11 and 12. Bioassays indicate that inserting the beta-bulge from IL-1beta confers partial signaling capability onto a K145D mutant of IL-1Ra. Based on the alignment, mutational assays and our computational folding results, we hypothesize that functional regions are not central to the beta-trefoil motif and cause slow folding. The IL-1beta beta-bulge facilitates activity and replacing it by the IL-1Ra beta-turn results in a hybrid protein that folds faster than IL-1beta. Inserting the beta11-beta12 connecting-loop, which aids inhibition, into either IL-1beta or the hybrid protein slows folding. Thus, regions that aid function (either through activity or inhibition) can be inferred from folding traps via structural differences. Mapping functional properties onto the numerous folds determined in structural genomics efforts is an area of intense interest. Our studies provide a systematic approach to mapping the functional genomics of a fold family.
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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.