Context-dependent contributions of backbone hydrogen bonding to β-sheet folding energetics

@article{Deechongkit2004ContextdependentCO,
  title={Context-dependent contributions of backbone hydrogen bonding to $\beta$-sheet folding energetics},
  author={Songpon Deechongkit and Houbi Nguyen and Evan T. Powers and Philip E. Dawson and Martin Gruebele and Jeffery W. Kelly},
  journal={Nature},
  year={2004},
  volume={430},
  pages={101-105}
}
Backbone hydrogen bonds (H-bonds) are prominent features of protein structures; however, their role in protein folding remains controversial because they cannot be selectively perturbed by traditional methods of protein mutagenesis. Here we have assessed the contribution of backbone H-bonds to the folding kinetics and thermodynamics of the PIN WW domain, a small β-sheet protein, by individually replacing its backbone amides with esters. Amide-to-ester mutations site-specifically perturb… 
The Role of Backbone Hydrogen Bonds in the Transition State for Protein Folding of a PDZ Domain
TLDR
Investigation of effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability finds native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding.
Conserved thermodynamic contributions of backbone hydrogen bonds in a protein fold.
TLDR
A comparative thermodynamic analysis of backbone hydrogen bonds in two proteins that adopt the same fold but are unrelated at the primary amino acid sequence level is reported, interpreted as evidence that the thermodynamics of backbone-backbone hydrogen-bonding interactions in a protein fold are conserved.
Understanding the mechanism of beta-sheet folding from a chemical and biological perspective.
TLDR
Current perspective on how structure acquisition is influenced by the sequence is reviewed, which determines local conformational propensities and mediates the hydrophobic effect, hydrogen bonding, and analogous intramolecular interactions is reviewed.
Direct analysis of backbone-backbone hydrogen bond formation in protein folding transition states.
TLDR
Results reveal that backbone-backbone hydrogen bonding interactions are formed in the beta-turn and alpha-helical transition state structures of ProtL and Arc repressor, respectively; and they were not form in the intersubunit beta-sheet interface of Arc repress, a region ofArc repressor's polypeptide chain previously shown to have other non-native-like conformations in Arc's protein folding transition state.
Backbone-Backbone H-Bonds Make Context-Dependent Contributions to Protein Folding Kinetics and Thermodynamics: Lessons from Amide-to-Ester Mutations.
TLDR
The use of amide-to-ester mutation as a tool to evaluate the contribution of backbone-backbone H-bonds to protein folding kinetics and thermodynamics is reviewed.
Probing the role of backbone hydrogen bonds in protein-peptide interactions by amide-to-ester mutations.
TLDR
This study systematically probed putative backbone hydrogen bonds between four different PDZ domains and peptides corresponding to natural protein ligands, demonstrating that hydrogen bonds contribute significantly to ligand binding and specifically addresses these for PDZ domain-peptide interactions.
Using thioamides to site-specifically interrogate the dynamics of hydrogen bond formation in β-sheet folding.
TLDR
It is shown that reducing the strength of the peptide's backbone-backbone H-bonds, except the one directly next to the β-turn, does not change the folding rate, suggesting that most native interstrand H-Bonds in β-hairpins are formed only after the folding transition state.
Probing the folding transition state structure of the villin headpiece subdomain via side chain and backbone mutagenesis.
TLDR
It is shown, using an amide-to-ester mutation strategy, that the formation of backbone hydrogen bonds within helices is not rate-limiting in the folding of the subdomain, thereby suggesting that such hydrogen bonds are unlikely to be formed en route from the denatured to the transition state.
β-Sheet folding mechanisms from perturbation energetics
Amide backbone and sidechain mutagenesis data can be used in combination with kinetic and thermodynamic measurements to understand the energetic contributions of backbone hydrogen bonding and the
Probing Backbone Hydrogen Bonds in Proteins by Amide‐to‐Ester Mutations
TLDR
This minireview showcases examples of how amide‐to‐ester mutations can be used to uncover pivotal roles of backbone‐mediated hydrogen bonds in protein recognition, folding, function, and structure.
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