ArticleJournal of the American Chemical Society2014
Ultrafast hydrogen exchange reveals specific structural events during the initial stages of folding of cytochrome c.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- FoldPAthreader: predicting protein folding pathway using a novel folding force field model derived from known protein universe.Genome biology · 2024Article
- Recent Advances in Protein Folding Pathway Prediction through Computational Methods.Current medicinal chemistry · 2024Review
- DMSO-Quenched H/D-Exchange 2D NMR Spectroscopy and Its Applications in Protein Science.Molecules (Basel, Switzerland) · 2022Review
- Advances in Mixer Design and Detection Methods for Kinetics Studies of Macromolecular Folding and Binding on the Microsecond Time Scale.Molecules (Basel, Switzerland) · 2022Article
- Dramatic Shape Changes Occur as CytochromeThe journal of physical chemistry. B · 2020Article
- Accurate Prediction of Amide Exchange in the Fast Limit Reveals Thrombin Allostery.Biophysical journal · 2019Article
- Chemical Exchange.Methods in enzymology · 2019Article
- Complex Folding Landscape of Apomyoglobin at Acidic pH Revealed by Ultrafast Kinetic Analysis of Core Mutants.The journal of physical chemistry. B · 2018Article
- Early Folding Events, Local Interactions, and Conservation of Protein Backbone Rigidity.Biophysical journal · 2016Article
- Start2Fold: a database of hydrogen/deuterium exchange data on protein folding and stability.Nucleic acids research · 2016Article
- Microfluidics: reframing biological enquiry.Nature reviews. Molecular cell biology · 2015Review
- How amide hydrogens exchange in native proteins.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
4 authors.
Funding
Abstract
Many proteins undergo a sharp decrease in chain dimensions during early stages of folding, prior to the rate-limiting step in folding. However, it remains unclear whether compact states are the result of specific folding events or a general hydrophobic collapse of the poly peptide chain driven by the change in solvent conditions. To address this fundamental question, we extended the temporal resolution of NMR-detected H/D exchange labeling experiments into the microsecond regime by adopting a microfluidics approach. By observing the competition between H/D exchange and folding as a function of labeling pH, coupled with direct measurement of exchange rates in the unfolded state, we were able to monitor hydrogen-bond formation for over 50 individual backbone NH groups within the initial 140 microseconds of folding of horse cytochrome c. Clusters of solvent-shielded amide protons were observed in two α-helical segments in the C-terminal half of the protein, while the N-terminal helix remained largely unstructured, suggesting that proximity in the primary structure is a major factor in promoting helix formation and association at early stages of folding, while the entropically more costly long-range contacts between the N- and C-terminal helices are established only during later stages. Our findings clearly indicate that the initial chain condensation in cytochrome c is driven by specific interactions among a subset of α-helical segments rather than a general hydrophobic collapse.
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