title: Autocatalytic folding of the folding catalyst FKBP12.
abstract: Prolyl isomerases are folding enzymes and thus have the potential to catalyze their own folding. We show here that the folding of cytosolic FKBP12 (FK 506 binding protein) is an autocatalytic process both for the mature protein and for a fusion protein with an amino-terminal extension of 16 residues. Native FKBP contains seven trans-prolyl peptide bonds, and the cis-to-trans isomerizations of some or all of them constitute the slow, rate-limiting events in folding. The rate of an autocatalytic reaction increases with reactant concentration, because the product catalyzes its own formation. Accordingly, the folding of the fusion protein was more than 10-fold accelerated when the protein concentration was increased from 0.05 microM to 10 microM. At high concentrations of both forms of FKBP12 autocatalysis was very efficient, and the observed folding rate seemed to approach the rate of the fast direct folding reaction of the protein molecules with the correct (all trans) peptidyl-prolyl bond conformation.
authors.affiliation: Biochemisches Laboratorium, Universität Bayreuth, D-95440 Bayreuth, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Scholz
authors.forename: T
authors.initials: T
authors.lastname: Zarnt
authors.forename: G
authors.initials: G
authors.lastname: Kern
authors.forename: K
authors.initials: K
authors.lastname: Lang
authors.forename: H
authors.initials: H
authors.lastname: Burtscher
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: F X
authors.initials: FX
authors.lastname: Schmid
mesh_terms: D000591:Amino Acid Isomerases / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002384:Catalysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D022021:Tacrolimus Binding Proteins
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins