The denatured state (the other half of the folding equation) and its role in protein stability

@article{Shortle1996TheDS,
  title={The denatured state (the other half of the folding equation) and its role in protein stability},
  author={David R. Shortle},
  journal={The FASEB Journal},
  year={1996},
  volume={10},
  pages={27 - 34}
}
  • D. Shortle
  • Published 1 January 1996
  • Chemistry, Medicine
  • The FASEB Journal
Experimental studies of the physical interactions that stabilize protein structure are complicated by the fact that proteins do not unfold to a simple reference state. When their folded structure breaks down, protein chains do not become random coils. Instead, they enter a poorly understood ensemble of partially folded states known collectively as the denatured state. Although it has long been held that agents that promote protein unfolding act specifically oh the denatured state, the idea that… 
Experimental characterization of the denatured state ensemble of proteins.
TLDR
The existence of residual structure in the DSE naturally leads to the question of its role in protein folding and stability, and raises the possibility that some mutations could exert a significant part of their effect by altering the D SE.
Perturbations of the denatured state ensemble: Modeling their effects on protein stability and folding kinetics
  • J. Wrabl, D. Shortle
  • Chemistry, Medicine
    Protein science : a publication of the Protein Society
  • 1996
TLDR
Stabilization of native interactions and imposition of gradients in the stability of local structure are two plausible mechanisms involving the denatured state that could play a role in the evolution of protein folding and stability.
Electrostatic interactions in the denatured state ensemble: their effect upon protein folding and protein stability.
TLDR
It is now recognized that the denatured state ensemble (DSE) of proteins can contain significant amounts of structure, particularly under native conditions, and electrostatic interactions play at most a minor role in the DSE.
Denatured state ensembles with the same radii of gyration can form significantly different long-range contacts.
TLDR
Long-range contacts and compactness in two apparently fully unfolded ensembles of the same protein: the acid unfolded state of the C-terminal domain of ribosomal protein L9 in the absence of high concentrations of urea as well as the urea unfolded state at low pH are analyzed.
Realistic modeling of the denatured states of proteins allows accurate calculations of the pH dependence of protein stability.
  • A. Elcock
  • Chemistry, Medicine
    Journal of molecular biology
  • 1999
TLDR
It is shown that by constructing atomistic models of the unfolded state with a simple molecular mechanics protocol that uses the native state as a starting point, much improved reproduction of pH effects on protein stability can be obtained.
Impact of Heat on Coil Hydrodynamic Size Yields the Energetics of Denatured State Conformational Bias.
TLDR
Though historically thought to give poor structural detail, the hydrodynamic size of the unfolded state is found to be an effective reporter on the extent of the biases for the α and PPII backbone conformations.
THE UNFOLDED PROTEIN STATE REVISITED
Most studies on proteins have centered on the conformation and stability of the folded state. The unfolded state has essentially been neglected because of its reputation of being devoid of biological
Simulations of the structural and dynamical properties of denatured proteins: the "molten coil" state of bovine pancreatic trypsin inhibitor.
TLDR
The unfolded structures of reduced bovine pancreatic trypsin inhibitor are in agreement with both past experiments suggesting that reduced BPTI is a random coil and more recent experiments providing evidence for non-random structure, demonstrating how ensembles of fluctuating structures can give rise to experimental observables that are seemingly at odds.
Probing the partly folded states of proteins by limited proteolysis.
TLDR
This review focuses on the use of proteolytic enzymes as probes of the structure and dynamics of folding intermediates and shows that this simple biochemical technique can provide useful information, complementing that obtained by other commonly used techniques and approaches.
Mutational analysis demonstrates that specific electrostatic interactions can play a key role in the denatured state ensemble of proteins.
TLDR
The characterization of highly specific electrostatic interactions in the denatured state of a small alpha-beta protein, the N-terminal domain of the ribosomal protein L9 (NTL9) is reported and it is proposed that these interactions are not encoded by local sequence effects but rather reflect interactions among residues more distant in sequence.
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