ArticleProceedings of the National Academy of Sciences of the United States of America2012
β-Bulge triggers route-switching on the functional landscape of interleukin-1β.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics.ACS chemical biology · 2024Article
- FcαRI binding at the IgA1 CProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Untangling the Influence of a Protein Knot on Folding.Biophysical journal · 2016Article
- Designed protein reveals structural determinants of extreme kinetic stability.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
- Comparing protein folding in vitro and in vivo: foldability meets the fitness challenge.Current opinion in structural biology · 2014Review
- Structural Consequences of Chromophore Formation and Exploration of Conserved Lid Residues amongst Naturally Occurring Fluorescent Proteins.Chemical physics · 2014Article
- β-Bulges: extensive structural analyses of β-sheets irregularities.Protein science : a publication of the Protein Society · 2013Article
- Altered backbone and side-chain interactions result in route heterogeneity during the folding of interleukin-1β (IL-1β).Biophysical journal · 2013Article
- Allosteric switching of agonist/antagonist activity by a single point mutation in the interluekin-1 receptor antagonist, IL-1Ra.Journal of molecular biology · 2013Article
- Design of a superior cytokine antagonist for topical ophthalmic use.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Hysteresis as a Marker for Complex, Overlapping Landscapes in Proteins.The journal of physical chemistry letters · 2013Article
- Understanding the folding-function tradeoff in proteins.PloS one · 2013Article
- Nonnative interactions regulate folding and switching of myristoylated protein.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Modulation of folding kinetics of repeat proteins: interplay between intra- and interdomain interactions.Biophysical journal · 2012Article
- Folding circular permutants of IL-1β: route selection driven by functional frustration.PloS one · 2012Article
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5 authors.
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Abstract
Proteins fold into three-dimensional structures in a funneled energy landscape. This landscape is also used for functional activity. Frustration in this landscape can arise from the competing evolutionary pressures of biological function and reliable folding. Thus, the ensemble of partially folded states can populate multiple routes on this journey to the native state. Although protein folding kinetics experiments have shown the presence of such routes for several proteins, there has been sparse information about the structural diversity of these routes. In addition, why a given protein populates a particular route more often than another protein of similar structure and sequence is not clear. Whereas multiple routes are observed in theoretical studies on the folding of interleukin-1β (IL-1β), experimental results indicate one dominant route where the central portion of the protein folds first, and is then followed by closure of the barrel in this β-trefoil fold. Here we show, using a combination of computation and experiment, that the presence of functionally important regions like the β-bulge in the signaling protein IL-1β strongly influences the choice of folding routes. By deleting the β-bulge, we directly observe the presence of route-switching. This route-switching provides a direct link between route selection and the folding and functional landscapes of a protein.
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