ArticleJournal of molecular biology2012
Conformational properties of the unfolded state of Im7 in nondenaturing conditions.
Article in Journal of molecular biology, 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, 29 citations in OpenAlex.
- Insights into the client protein release mechanism of the ATP-independent chaperone Spy.Nature communications · 2022Article
- Noyes-Whitney Dissolution Model-Based pH-Sensitive Slow Release of Paclitaxel (Taxol) from Human Hair-Derived Keratin Microparticle Carriers.BioMed research international · 2021Article
- Binding-induced folding under unfolding conditions: Switching between induced fit and conformational selection mechanisms.The Journal of biological chemistry · 2019Article
- Conformational flexibility within the nascent polypeptide-associated complex enables its interactions with structurally diverse client proteins.The Journal of biological chemistry · 2018Article
- Molecular recognition and packing frustration in a helical protein.PLoS computational biology · 2017Article
- A molecular mechanism of chaperone-client recognition.Science advances · 2016Article
- Forces Driving Chaperone Action.Cell · 2016Article
- Visualizing chaperone-assisted protein folding.Nature structural & molecular biology · 2016Article
- Substrate protein folds while it is bound to the ATP-independent chaperone Spy.Nature structural & molecular biology · 2016Article
- Using hydroxyl radical footprinting to explore the free energy landscape of protein folding.Methods (San Diego, Calif.) · 2015Article
- Native contact density and nonnative hydrophobic effects in the folding of bacterial immunity proteins.PLoS computational biology · 2015Article
- Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?Archives of biochemistry and biophysics · 2014Review
- A maximum entropy approach to the study of residue-specific backbone angle distributions in α-synuclein, an intrinsically disordered protein.Protein science : a publication of the Protein Society · 2014Article
- Energetically significant networks of coupled interactions within an unfolded protein.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Conformational dynamics is more important than helical propensity for the folding of the all α-helical protein Im7.Protein science : a publication of the Protein Society · 2013Article
- Tryptophan stabilizes His-heme loops in the denatured state only when it is near a loop end.Biochemistry · 2012Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The unfolded ensemble in aqueous solution represents the starting point of protein folding. Characterisation of this species is often difficult since the native state is usually predominantly populated at equilibrium. Previous work has shown that the four-helix protein, Im7 (immunity protein 7), folds via an on-pathway intermediate. While the transition states and folding intermediate have been characterised in atomistic detail, knowledge of the unfolded ensemble under the same ambient conditions remained sparse. Here, we introduce destabilising amino acid substitutions into the sequence of Im7, such that the unfolded state becomes predominantly populated at equilibrium in the absence of denaturant. Using far- and near-UV CD, fluorescence, urea titration and heteronuclear NMR experiments, we show that three amino acid substitutions (L18A-L19A-L37A) are sufficient to prevent Im7 folding, such that the unfolded state is predominantly populated at equilibrium. Using measurement of chemical shifts, (15)N transverse relaxation rates and sedimentation coefficients, we show that the unfolded species of L18A-L19A-L37A deviates significantly from random-coil behaviour. Specifically, we demonstrate that this unfolded species is compact (R(h)=25 Å) relative to the urea-denatured state (R(h)≥30 Å) and contains local clusters of hydrophobic residues in regions that correspond to the four helices in the native state. Despite these interactions, there is no evidence for long-range stabilising tertiary interactions or persistent helical structure. The results reveal an unfolded ensemble that is conformationally restricted in regions of the polypeptide chain that ultimately form helices I, II and IV in the native state.
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