Peptidyl-prolyl cis-trans isomerase improves the efficiency of protein disulfide isomerase as a catalyst of protein folding.

The cis-trans isomerization of prolyl peptide bonds and the formation of disulfide bonds are both slow steps in protein folding. By using ribonuclease T1 as a model system, we show that these two processes can become linked in the oxidative folding of reduced proteins and that the formation of the correct disulfide bonds is facilitated in the presence of peptidyl-prolyl cis-trans isomerase. In particular, the efficiency of protein disulfide isomerase (EC 5.3.4.1) as a catalyst of disulfide bond formation in the course of oxidative folding is markedly improved when peptidyl-prolyl cis-trans isomerase is present simultaneously. Possibly, unfolded or partially folded protein chains with correct prolyl isomers are better substrates for catalysis by protein disulfide isomerase. The interdependence of the two enzymatic activities detected during in vitro folding experiments could be of importance for the de novo folding and disulfide bond formation of nascent proteins in the endoplasmic reticulum.

[1]  M. Godbout,et al.  An endoplasmic reticulum-specific cyclophilin , 1991, Molecular and cellular biology.

[2]  N. Takahashi,et al.  Catalysis of protein folding by cyclophilins from different species. , 1991, The Journal of biological chemistry.

[3]  B. Davis.  DISC ELECTROPHORESIS – II METHOD AND APPLICATION TO HUMAN SERUM PROTEINS * , 1964, Annals of the New York Academy of Sciences.

[4]  F. Schmid,et al.  Catalysis of protein folding by prolyl isomerase , 1987, Nature.

[5]  T. Hayano,et al.  Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin , 1989, Nature.

[6]  R. Timpl,et al.  Folding mechanism of the triple helix in type-III collagen and type-III pN-collagen. Role of disulfide bridges and peptide bond isomerization. , 1980, European journal of biochemistry.

[7]  C. Pace,et al.  Conformational stability and activity of ribonuclease T1 with zero, one, and two intact disulfide bonds. , 1988, The Journal of biological chemistry.

[8]  C. Zuker,et al.  The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins , 1991, Cell.

[9]  C. Epstein,et al.  Acceleration of reactivation of reduced bovine pancreatic ribonuclease by a microsomal system from rat liver. , 1963, The Journal of biological chemistry.

[10]  U. Hahn,et al.  Replacement of a cis proline simplifies the mechanism of ribonuclease T1 folding. , 1990, Biochemistry.

[11]  E. Eikenberry,et al.  Formation of the triple helix of type I procollagen in cellulo. Temperature-dependent kinetics support a model based on cis in equilibrium trans isomerization of peptide bonds. , 1984, European journal of biochemistry.

[12]  F. Schmid,et al.  Protein-disulphide isomerase and prolyl isomerase act differently and independently as catalysts of protein folding , 1988, Nature.

[13]  H. Lodish,et al.  Cyclosporin A inhibits an initial step in folding of transferrin within the endoplasmic reticulum. , 1991, The Journal of biological chemistry.

[14]  R. Freedman,et al.  Defective co-translational formation of disulphide bonds in protein disulphide-isomerase-deficient microsomes , 1988, Nature.

[15]  F. B. Straub,et al.  The enzymic reactivation of reduced ribonuclease. , 1963, Biochimica et biophysica acta.

[16]  T. Creighton,et al.  The disulphide folding pathway of ribonuclease T1. , 1986, Journal of molecular biology.

[17]  G. Fischer,et al.  [Determination of enzymatic catalysis for the cis-trans-isomerization of peptide binding in proline-containing peptides]. , 1984, Biomedica biochimica acta.

[18]  R. Freedman,et al.  Structural properties of homogeneous protein disulphide-isomerase from bovine liver purified by a rapid high-yielding procedure. , 1983, The Biochemical journal.

[19]  N. Takahashi,et al.  Two distinct forms of peptidylprolyl-cis-trans-isomerase are expressed separately in periplasmic and cytoplasmic compartments of Escherichia coli cells. , 1991, Biochemistry.

[20]  T. Kiefhaber,et al.  Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins , 1989, Nature.

[21]  Stuart L. Schreiber,et al.  Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes , 1991, Cell.

[22]  U. Heinemann,et al.  Specific protein-nucleic acid recognition in ribonuclease T1–2′-guanylic acid complex: an X-ray study , 1982, Nature.

[23]  A. Superti-Furga,et al.  Cyclosporin A slows collagen triple-helix formation in vivo: indirect evidence for a physiologic role of peptidyl-prolyl cis-trans-isomerase. , 1991, The Journal of biological chemistry.

[24]  B. Haendler,et al.  A novel secreted cyclophilin-like protein (SCYLP). , 1991, The Journal of biological chemistry.

[25]  P. Caroni,et al.  S-cyclophilin. New member of the cyclophilin family associated with the secretory pathway. , 1991, The Journal of biological chemistry.

[26]  C. Walsh,et al.  Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Schreiber,et al.  Chemistry and biology of the immunophilins and their immunosuppressive ligands. , 1991, Science.

[28]  J. Brandts,et al.  Catalysis of proline isomerization during protein-folding reactions. , 1988, Biochimica et biophysica acta.

[29]  U. Hahn,et al.  Folding of ribonuclease T1. 1. Existence of multiple unfolded states created by proline isomerization. , 1990, Biochemistry.

[30]  G. Crabtree,et al.  Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A , 1991, Nature.