ArticleProceedings of the National Academy of Sciences of the United States of America2013
Probing the protein-folding mechanism using denaturant and temperature effects on rate constants.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 39 citations in OpenAlex.
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- Experimentally determined strengths of favorable and unfavorable interactions of amide atoms involved in protein self-assembly in water.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Using Single-Molecule Chemo-Mechanical Unfolding to Simultaneously Probe Multiple Structural Parameters in Protein Folding.Methods and protocols · 2019Article
- A small single-domain protein folds through the same pathway on and off the ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water.Biochemistry · 2018Article
- The mechanism and high-free-energy transition state of lac repressor-lac operator interaction.Nucleic acids research · 2017Article
- Partially native intermediates mediate misfolding of SOD1 in single-molecule folding trajectories.Nature communications · 2017Article
- Experimental Atom-by-Atom Dissection of Amide-Amide and Amide-Hydrocarbon Interactions in HJournal of the American Chemical Society · 2017Article
- Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Basis of Protein Stabilization by K Glutamate: Unfavorable Interactions with Carbon, Oxygen Groups.Biophysical journal · 2016Article
- TMAO-Protein Preferential Interaction Profile Determines TMAO's Conditional In Vivo Compatibility.Biophysical journal · 2016Article
- Introduction of a polar core into the de novo designed protein Top7.Protein science : a publication of the Protein Society · 2016Article
- Positioning the Intracellular Salt Potassium Glutamate in the Hofmeister Series by Chemical Unfolding Studies of NTL9.Biochemistry · 2016Article
- Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Single-molecule chemo-mechanical unfolding reveals multiple transition state barriers in a small single-domain protein.Nature communications · 2015Article
- Dispersion interactions between urea and nucleobases contribute to the destabilization of RNA by urea in aqueous solution.The journal of physical chemistry. B · 2015Article
- Using solutes and kinetics to probe large conformational changes in the steps of transcription initiation.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Benchmarking all-atom simulations using hydrogen exchange.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein folding has been extensively studied, but many questions remain regarding the mechanism. Characterizing early unstable intermediates and the high-free-energy transition state (TS) will help answer some of these. Here, we use effects of denaturants (urea, guanidinium chloride) and temperature on folding and unfolding rate constants and the overall equilibrium constant as probes of surface area changes in protein folding. We interpret denaturant kinetic m-values and activation heat capacity changes for 13 proteins to determine amounts of hydrocarbon and amide surface buried in folding to and from TS, and for complete folding. Predicted accessible surface area changes for complete folding agree in most cases with structurally determined values. We find that TS is advanced (50-90% of overall surface burial) and that the surface buried is disproportionately amide, demonstrating extensive formation of secondary structure in early intermediates. Models of possible pre-TS intermediates with all elements of the native secondary structure, created for several of these proteins, bury less amide and hydrocarbon surface than predicted for TS. Therefore, we propose that TS generally has both the native secondary structure and sufficient organization of other regions of the backbone to nucleate subsequent (post-TS) formation of tertiary interactions. The approach developed here provides proof of concept for the use of denaturants and other solutes as probes of amount and composition of the surface buried in coupled folding and other large conformational changes in TS and intermediates in protein processes.
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