On the relevance of non-random polypeptide conformations for protein folding.
The possibility that any non-random conformation in reduced bovine pancreatic trypsin inhibitor (BPTI) and ribonuclease A might be significant for folding has been considered, using the experimental data available on forming the first disulphide bond in each. It is a thermodynamic necessity that whatever conformation stabilises a particular disulphide bond be stabilised to the same extent by the presence of the disulphide. The stabilising effects of disulphides are known approximately, so the stability of any non-random conformation found in a one-disulphide intermediate can be estimated in the absence of the disulphide bond. The non-random conformation in the BPTI intermediates is sufficiently labile to indicate that it would be expected to be present in no more than 5% of the reduced BPTI molecules. There is much less non-random conformation apparent in ribonuclease A. Whatever conformations are represented in the bulk of these two reduced proteins cannot favour disulphide formation and further productive folding.
Creighton
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TE
Medical Research Council Laboratory of Molecular Biology, Cambridge, U.K.
D007611:Aprotinin; D007700:Kinetics; D008962:Models, Theoretical; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic; D014508:Urea
D014508:Urea; D007611:Aprotinin; D012259:Ribonuclease, Pancreatic