Unfolded proteins backbone conformations

Turning now to the chapters in this volume, a variety of complementary techniques and approaches have been used to characterize peptide and protein unfolding induced by temperature, pressure, and solvent. Our goal has been to assemble these complementary views within a single volume in order to develop a more complete picture of denatured peptides and proteins. The unifying observation in common to all chapters is the detection of preferred backbone conformations in experimentally accessible unfolded states. 

IS POLYPROLINE II A MAJOR BACKBONE CONFORMATION IN UNFOLDED PROTEINS ... 

Protein stability is just the difference in free energy between the correctly folded structure of a protein and the unfolded, denatured form. In the denatured form, the protein is unfolded, side chains and the peptide backbone are exposed to water, and the protein is conformationally mobile (moving around between a lot of different, random structures). The more stable the protein, the larger the free energy difference between the unfolded form and the native structure. 

Shi Z, Woody RW, Kallenbach NR (2002) Is polyproline II a major backbone conformation in unfolded proteins In Unfolded Proteins, Rose G, ed, Adv Protein Chem 62 163-240... 

Fig. 7.2 (A) Protein folding. The small Trpcage protein in an unfolded conformation (left) and its stable, folded conformation (right). The protein backbone is shown in a simpMed, green, tube/ribbon representation. A single, tryptophan sidechain is also shown, which forms the core of the folded structure. (B) Folded proteins. Space-filhng views of cytochrome c (an electron carrier in the respiratory chain) and hemoglobin (an oxygen carrier in the blood), along with a water molecule, approximately to scale...

CD has found many applications in the study of protein folding.Its ability to monitor both the overall backbone conformation (far-UV) and the environment of one or more specific side-chain chromophores (near-UV) has made CD a favorite method for following protein folding and unfolding (denaturation). 

Nodet G et al (2009) Quantitative description of backbone conformational sampling of unfolded proteins at amino acid resolution from NMR residual dipolar couplings. J Am Chem Soc 131(49) 17908-17918... 

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