ArticleProtein science : a publication of the Protein Society2012
Experimental support for the foldability-function tradeoff hypothesis: segregation of the folding nucleus and functional regions in fibroblast growth factor-1.
Article in Protein science : a publication of the Protein Society, 2012. 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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14 citing papers in PubMed, 21 citations in OpenAlex.
- Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency.Scientific reports · 2023Article
- Decoding an Amino Acid Sequence to Extract Information on Protein Folding.Molecules (Basel, Switzerland) · 2022Review
- Functionalization of a symmetric protein scaffold: Redundant folding nuclei and alternative oligomeric folding pathways.Protein science : a publication of the Protein Society · 2022Article
- Cooperative hydrophobic core interactions in the β-trefoil architecture.Protein science : a publication of the Protein Society · 2021Article
- Oligomerization of a symmetric β-trefoil protein in response to folding nucleus perturbation.Protein science : a publication of the Protein Society · 2020Article
- Ab initio folding of a trefoil-fold motif reveals structural similarity with a β-propeller blade motif.Protein science : a publication of the Protein Society · 2020Article
- Investigating the dynamics and polyanion binding sites of fibroblast growth factor-1 using hydrogen-deuterium exchange mass spectrometry.Protein science : a publication of the Protein Society · 2018Article
- Folding nucleus structure persists in thermally-aggregated FGF-1.Protein science : a publication of the Protein Society · 2018Article
- An S116R Phosphorylation Site Mutation in Human Fibroblast Growth Factor-1 Differentially Affects Mitogenic and Glucose-Lowering Activities.Journal of pharmaceutical sciences · 2016Article
- Why reinvent the wheel? Building new proteins based on ready-made parts.Protein science : a publication of the Protein Society · 2016Review
- Evolution of a protein folding nucleus.Protein science : a publication of the Protein Society · 2016Article
- Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles.PLoS computational biology · 2015Article
- A single aromatic core mutation converts a designed "primitive" protein from halophile to mesophile folding.Protein science : a publication of the Protein Society · 2015Article
- Protein Science "Best Paper" awards to Youngil Chang and Liam Longo.Protein science : a publication of the Protein Society · 2013Article
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3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The acquisition of function is often associated with destabilizing mutations, giving rise to the stability-function tradeoff hypothesis. To test whether function is also accommodated at the expense of foldability, fibroblast growth factor-1 (FGF-1) was subjected to a comprehensive φ-value analysis at each of the 11 turn regions. FGF-1, a β-trefoil fold, represents an excellent model system with which to evaluate the influence of function on foldability: because of its threefold symmetric structure, analysis of FGF-1 allows for direct comparisons between symmetry-related regions of the protein that are associated with function to those that are not; thus, a structural basis for regions of foldability can potentially be identified. The resulting φ-value distribution of FGF-1 is highly polarized, with the majority of positions described as either folded-like or denatured-like in the folding transition state. Regions important for folding are shown to be asymmetrically distributed within the protein architecture; furthermore, regions associated with function (i.e., heparin-binding affinity and receptor-binding affinity) are localized to regions of the protein that fold after barrier crossing (late in the folding pathway). These results provide experimental support for the foldability-function tradeoff hypothesis in the evolution of FGF-1. Notably, the results identify the potential for folding redundancy in symmetric protein architecture with important implications for protein evolution and design.
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