title: Disulphide-coupled protein folding pathways.
abstract: Protein folding pathways that involve disulphide bond formation can be determined in great detail. Those of bovine pancreatic trypsin inhibitor, alpha-lactalbumin and ribonucleases A and T1 are compared and contrasted. In each species, whatever conformation favours one disulphide bond over another is stabilized to the same extent by the presence of that disulphide bond in the disulphide intermediates. The pathways differ markedly in the nature of that conformation: in bovine pancreatic trypsin inhibitor a crucial intermediate is partly folded, in alpha-lactalbumin the intermediates tend to adopt to varying extents the molten globule conformation, while in the ribonucleases the early disulphide intermediates are largely unfolded, and none predominate. In each case, however, the slowest step is formation of a disulphide bond that will be buried in a stable folded conformation; the most rapid step is formation of an accessible disulphide bond on the surface of a folded conformation. Quasi-native species with the native conformation, but incomplete disulphide bonds, can either increase or decrease the rate of further disulphide formation.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Creighton
mesh_terms: D000818:Animals; D002417:Cattle; D004220:Disulfides / Q000737:chemistry*; D005095:Exoribonucleases / Q000737:chemistry*; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry*; D010194:Pancreatin / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
chemical_list: D004220:Disulfides; D010940:Plant Proteins; D014361:Trypsin Inhibitors; D010194:Pancreatin; D007768:Lactalbumin; D005095:Exoribonucleases; C042081:exoribonuclease T; D012259:Ribonuclease, Pancreatic; D000516:alpha-Amylases