ArticleProceedings of the National Academy of Sciences of the United States of America2008
Backtracking on the folding landscape of the beta-trefoil protein interleukin-1beta?
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. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- How soluble misfolded proteins bypass chaperones at the molecular level.Nature communications · 2023Pooled it
- A widespread protein misfolding mechanism is differentially rescued in vitro by chaperones based on gene essentiality.Nature communications · 2025Article
- A widespread protein misfolding mechanism is differentially rescued by chaperones based on gene essentiality.bioRxiv : the preprint server for biology · 2025Article
- Protein misfolding involving entanglements providesa structural explanation for the origin of stretched-exponential refolding kinetics.Science advances · 2025Article
- The Protein Folding Problem: The Role of Theory.Journal of molecular biology · 2021Review
- Cooperative hydrophobic core interactions in the β-trefoil architecture.Protein science : a publication of the Protein Society · 2021Article
- Simultaneous Assignment and Structure Determination of Proteins From Sparsely Labeled NMR Datasets.Frontiers in molecular biosciences · 2021Article
- Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase.eLife · 2020Article
- NMR-assisted protein structure prediction with MELDxMD.Proteins · 2019Article
- Versatile format of minichaperone-based protein fusion system.Scientific reports · 2019Article
- Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions.Annual review of biophysics · 2018Article
- Engineering carboxypeptidase G2 circular permutations for the design of an autoinhibited enzyme.Protein engineering, design & selection : PEDS · 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
- Protein knotting through concatenation significantly reduces folding stability.Scientific reports · 2016Article
- Blind protein structure prediction using accelerated free-energy simulations.Science advances · 2016Article
- Evolution of a protein folding nucleus.Protein science : a publication of the Protein Society · 2016Article
- Accelerating molecular simulations of proteins using Bayesian inference on weak information.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- 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
- Knotted proteins: A tangled tale of Structural Biology.Computational and structural biotechnology journal · 2015Review
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4 authors.
Funding
Abstract
Interleukin-1beta (IL-1beta) is a cytokine within the beta-trefoil family. Our data indicate that the folding/unfolding routes are geometrically frustrated. Follow-up theoretical studies predicted backtracking events that could contribute to the broad transition barrier and the experimentally observed long-lived intermediate. The backtracking route is attributed to the topological frustration introduced by the packing of the functional loop (the beta-bulge, residues 47-53) to the nascent barrel. We used real-time refolding NMR experiments to test for the presence of backtracking events predicted from our theoretical studies. Structural variants of IL-1beta, a beta-bulge deletion, and a circular permutation that opens the protein in the middle of the experimentally observed kinetic intermediate, were also refolded and studied to determine the affects on the observed folding reactions. The functional loop deletion variant demonstrated less backtracking than in WT protein whereas the permutation still maintains backtracking in agreement with theoretical predictions. Taken together, these findings indicate that the backtracking results from geometric frustration introduced into the fold for functional purposes.
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