title: Hydrophobic interactions accelerate early stages of the folding of BPTI.
abstract: Bovine pancreatic trypsin inhibitor (BPTI) has long served as an important model system for the studies of the protein folding process. Recently a kinetically important folding intermediate has been detected early on the oxidative folding pathway of BPTI [Dadlez, M., & Kim, P. S. (1995) Nat. Struct. Biol. 2, 674-679]. The intermediate, named [14-38], contains a single native disulfide bond between residues 14 and 38, and forms much faster than any other single-disulfide intermediate. A series of 24 mutants of BPTI has been studied here to detect amino acids which contribute to fast formation of [14-38]. Seven nonpolar or aromatic residues, distant from the cysteines by as many as eight residues, are found to accelerate the formation of 14-38 disulfide, without changing the reactivities of the cysteines. The acceleration is observed even in 8 M urea. It is concluded that in the early stages of the folding of BPTI and BPTI-like domains, the residual structure of the denatured state promotes native pairing of cysteines by way of interaction of hydrophobic residues. A similar mechanism may facilitate early steps in the folding of proteins in general.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa.
authors.forename: M
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010084:Oxidation-Reduction; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D011994:Recombinant Proteins; D007611:Aprotinin; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide