ArticleProceedings of the National Academy of Sciences of the United States of America2007
Probing a moving target with a plastic unfolding intermediate of an ankyrin-repeat protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.The Journal of biological chemistry · 2026Article
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.bioRxiv : the preprint server for biology · 2026Article
- Cooperative mechanics of PR65 scaffold underlies the allosteric regulation of the phosphatase PP2A.Structure (London, England : 1993) · 2023Article
- Evolution and folding of repeat proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Engineering and exploiting synthetic allostery of NanoLuc luciferase.Nature communications · 2022Article
- Resolving the fine structure in the energy landscapes of repeat proteins.QRB discovery · 2022Article
- Reversible folding energetics of Yersinia Ail barrel reveals a hyperfluorescent intermediate.Biochimica et biophysica acta. Biomembranes · 2020Article
- Folding cooperativity and allosteric function in the tandem-repeat protein class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Disorder drives cooperative folding in a multidomain protein.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.Journal of molecular biology · 2016Article
- Single-molecule FRET reveals hidden complexity in a protein energy landscape.Structure (London, England : 1993) · 2015Article
- Folding pathway of a multidomain protein depends on its topology of domain connectivity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
- Diffuse transition state structure for the unfolding of a leucine-rich repeat protein.Physical chemistry chemical physics : PCCP · 2014Article
- Loop interactions and dynamics tune the enzymatic activity of the human histone deacetylase 8.Journal of the American Chemical Society · 2013Article
- Complex energy landscape of a giant repeat protein.Structure (London, England : 1993) · 2013Article
- Mechanical properties of β-catenin revealed by single-molecule experiments.Biophysical journal · 2012Article
- Modulation of folding kinetics of repeat proteins: interplay between intra- and interdomain interactions.Biophysical journal · 2012Article
- Mechanical anisotropy of ankyrin repeats.Biophysical journal · 2012Article
- Modulation of the multistate folding of designed TPR proteins through intrinsic and extrinsic factors.Protein science : a publication of the Protein Society · 2012Article
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Abstract
Repeat proteins are composed of tandem arrays of 30- to 40-residue structural motifs and are characterized by short-range interactions between residues close in sequence. Here we have investigated the equilibrium unfolding of D34, a 426-residue fragment of ankyrinR that comprises 12 ankyrin repeats. We show that D34 unfolds via an intermediate in which the C-terminal half of the protein is structured and the N-terminal half is unstructured. Surprisingly, however, we find that we change the unfolding process when we attempt to probe it. Single-site, moderately destabilizing mutations at the C terminus result in different intermediates dominating. The closer to the C terminus the mutation, the fewer repeats are structured in the intermediate; thus, structure in the intermediate frays from the site of the mutation. This behavior contrasts with the robust unfolding of globular proteins in which mutations can destabilize an intermediate but do not cause a different intermediate to be populated. We suggest that, for large repeat arrays, the energy landscape is very rough, with many different low-energy species containing varying numbers of folded modules so the species that dominates can be altered easily by single, conservative mutations. The multiplicity of partly folded states populated in the equilibrium unfolding of D34 is also mirrored by the kinetic folding mechanism of ankyrin-repeat proteins in which we have observed that parallel pathways are accessible from different initiation sites in the structure.
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