Folding intermediates

Ducin Y and P A Kollrtran 1998. Pathways to a Protein Folding Intermediate Observed in Microsecond Simulation in Aqueous Solution. Science 282 740-744. 

Y Duan, PA Kollman. Pathways to a protein folding intermediate observed in a 1-microsecond simulation m aqueous solution. Science 282 740-744, 1998. 

In the native protein these less stable ds-proline peptides are stabilized by the tertiary structure but in the unfolded state these constraints are relaxed and there is an equilibrium between ds- and trans-isomers at each peptide bond. When the protein is refolded a substantial fraction of the molecules have one or more proline-peptide bonds in the incorrect form and the greater the number of proline residues the greater the fraction of such molecules. Cis-trans isomerization of proline peptides is intrinsically a slow process and in vitro it is frequently the rate-limiting step in folding for those molecules that have been trapped in a folding intermediate with the wrong isomer. 

The way in which molecular chaperones interact with polypeptides during the folding process is not completely understood. What is clear is that chaperones bind effectively to the exposed hydrophobic regions of partially folded structures. These folding intermediates are less compact than the native folded proteins. They contain large amounts of secondary and even some tertiary... 

Raschke, T. M., and Marqnsee, S., 1997. The kinetic folding intermediate of ribonnclease H resembles the acid molten globule and partially unfolded molecules detected under native conditions. Nature Structural Biology 4 298-304. 

Khandogin J, Raleigh DP, Brooks CL III (2007) Folding intermediate in the villin headpiece domain arises from disruption of a N-terminal hydrogen-bonded network. J Am Chem Soc 129 3056-3057. 

Evans, P. A., and Radford, S. E. (1994). Probing the structure of folding intermediates. Curr. Opin. Strud. Biol. 4, 100-106. 

Baldwin, R. L. (1991). Molten globule Specific and non-specific folding intermediates Chemtracts Biochem. Mol. Biol. 2, 379-389. 

Zhu, L., Zhang, X. J., Wang, L. Y., Zhou, J. M., and Perrett, S. (2003). Relationship between stability of folding intermediates and amyloid formation for the yeast prion Ure2p A quantitative analysis of the effects of pH and buffer system./ Mol. Biol. 328, 235-254. 

H. Krebs, F. X. Schmid, and R. Jaenicke, Native-like folding intermediates of homologous ribonucleases, Biochemistry 24, 3846-3852 (1985). 

The most characteristic features of this proposed folding scheme are the proposal of different kinds of nucleation for the different major structure types, the postulation of some rather large-scale concerted folding units, and the prediction of folding intermediates with somewhat greater amounts of the same sort of secondary structure found in the final native protein. The last effect might turn out to be most pronounced in those proteins with very irregular secondary structures. 

Uversky, V.N., A.S. Kamoup, D.J. Segel, S. Seshadri, S. Doniach, and A.L. Fink. 1998. Anion-induced folding of Staphylococcal nuclease characterization of multiple equilibrium partially folded intermediates. J Mol Biol 278 879-894. 

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