Protein disulfide isomerase: Multiple roles in the modification of nascent secretory proteins

Freedman, Robert B.

doi:10.1016/0092-8674(89)90043-3

Cited by 466 publications

(248 citation statements)

References 18 publications

Supporting

Mentioning

239

Contrasting

Unclassified

Order By: Relevance

“…Thus, a general role of hsp60 for protein folding in vivo appears possible. A number of other proteins were identified which assist protein folding in vivo (ROTHMAN 1989;FISCHER and SCHMID 1990; for a review), including c/s/frans-peptidyl-prolylisomerase (LANG et al 1987) and the protein disulfide isomerase (FREEDMAN 1989). Within the thermodynamic limits chaperonins and these other proteins may assist folding at a kinetic level.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Langer¹,

Neupert²

1991

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Langer¹,

Neupert²

1991

Current Topics in Microbiology and Immunology

View full text Add to dashboard Cite

“…This is consistent with the localization and function of both enzymes in the cell. Eukaryotic PDI is located in the lumen of the ER, where it catalyzes oxidative protein folding, i.e., the formation of disulfide bonds of secretory proteins (Bulleid & Freedman, 1988;Freedman, 1989;Noiva & Lennarz, 1992). Thioredoxin occurs in the cytoplasm of bacterial and eukaryotic cells where the redox conditions are reducing and where the protein is involved in regulation of protein activity by catalysis of NADPH-dependent reductions of functional disulfide bonds (Holmgren, 1985(Holmgren, , 1989.…”

Section: ~--mentioning

confidence: 99%

Redox properties of protein disulfide isomerase (dsba) from escherichia coli

1993

View full text Add to dashboard Cite

The redox properties of periplasmic protein disulfide isomerase (DsbA) from Escherichia coli were analyzed by measuring the equilibrium constant of the oxidation of reduced DsbA by oxidized glutathione. The experiments are based on the finding that the intrinsic tryptophan fluorescence of DsbA increases about threefold upon reduction of the enzyme, which can be explained by the catalytic disulfide bridge quenching the fluorescence of a neighboring tryptophan residue. From the specific fluorescence of DsbA equilibrated in the presence of different ratios of reduced gnd oxidized glutathione at pH 7, an equilibrium constant of 1.2 X M was determined, corresponding to a standard redox potential ( E ; ) of DsbA of -0.089 V. Thus, DsbA is a significantly stronger oxidant than cytoplasmic thioredoxins and its redox properties are similar to those of eukaryotic protein disulfide isomerase. The equilibrium constants for the DsbA/glutathione equilibrium were found to be strongly dependent on pH and varied from 2.5 x lop3 M to 3.9 x M between pH 4 and 8.5. The redox state-dependent fluorescence properties of DsbA should allow detailed physicochemical studies of the enzyme as well as the quantitative determination of the oxidized protein by fluorescence titration with dithiothreitol and open the possibility to observe bacterial protein disulfide isomerase "at work" during catalysis of oxidative protein folding.Keywords: disulfide interchange; dithiothreitol; DsbA protein; Escherichia coli; glutathione; protein disulfide isomerase; redox potentialThe formation of disulfide bonds in the periplasmic space of Escherichia coli is catalyzed by the DsbA protein (Bardwell et al., 1991;Kamitani et al., 1992). This recently discovered PDI consists of 189 residues with two cysteines comprising the catalytic disulfide bridge. The enzyme does not exhibit an overall sequence homology to cytoplasmic thioredoxin of E. coli and the well-characterized eukaryotic PDI located in the ER. However, DsbA shares a common active site with oxidoreductases such as PDI, thioredoxin, and glutaredoxin, as the active cysteines are separated by only two residues and the amino acid sequences surrounding the active disulfide are similar in all these enzymes (Bardwell et al., 1991). The intrinsic redox potentials of thioredoxins and eukaryotic PDI have been determined and were found to be in the range of -0.26 V to .-0.23 V and -0

show abstract

“…Already in the lumen of the endoplasmatic reticulum, disulfide bonds are formed perhaps catalyzed by the protein disulfide isomerase (Freedman, 1989). In the secretory pathway of the casein micelle later formation of disulfide bonds is also possible catalyzed by sulfhydryl oxidase.…”

Section: Discussionmentioning

confidence: 99%

Localization of two interchain disulfide bridges in dimers of bovine α_s2‐casein

Rasmussen¹,

Højrup²,

Petersen

1992

European Journal of Biochemistry

View full text Add to dashboard Cite

Carboxymethylation of bovine skimmed milk with 14C-labelled iodoacetic acid followed by purification of the a,,-casein dimer showed that all four cysteine residues in the protein are engaged in disulfide linkages. Mass spectrometry and sequence analysis of cystine-containing tryptic peptides revealed the presence of two interchain disulfide bridges in the protein. Sequence analysis of disulfidelinked peptides resulting from an enzymatic cleavage between the bridges demonstrated that the individual chains in the dimers are either aligned in an antiparallel or a parallel orientation. The identity of some of the disulfide-linked peptides was further verified by performic acid oxidation followed by sequence analysis of the resulting peptides.The caseins are the predominant proteins synthesized in the mammary gland and occur in milk as large stable calcium phosphate -protein complexes termed micelles. As well as being the prime source of amino acids, the casein micelle serves as a carrier of calcium phosphate, thus providing the neonate with a source of calcium and phosphate for bone formation. In milk the casein micelles are maintained in a stable colloidal dispersion. However, when the C-terminal part of rc-casein is cleaved off by chymosin, the micelles become insoluble and a coagulation process occurs. In bovine milk the micelles are composed of four caseins aSl-, as,-, p-and rc-casein whose amino acid sequences have been determined at the protein level (Mercier et al., 1971(Mercier et al., , 1973Ribadeau Dumas et al., 1972;Brignon et al., 1977) and at the cDNA level (Stewart et al., 1984(Stewart et al., , 1987.There is no generally accepted model of the micelle although it is believed that the smaller submicelles are used as building blocks (Farrell, 1988). A characteristic feature of the caseins is their high content of phosphorylated seryl residues which are located in specific phosphorylation site motifs (Holt and Sawyer, 1988; Kemp and Pearson, 1990) and are essential for the interaction with inorganic calcium phosphate. The caseins have been divided into two classes according to their sensitivity to precipitation by Ca2+ (Waugh, 1971). a,,-Casein which belongs to the calcium-sensitive group comprises four components previously designated as a,,-, aS3-, as4 and as6-casein (Annan and Manson, 1969). These components have identical amino acid sequences (207 residues) but differ in their phosphate content (Brignon et al., 1976). Of the four caseins only a,,-casein and rc-casein contain cysteines. In JCcasein they are used in multimerization (Talbot and Waugh, 1970) whereas it has been reported that a,,-casein naturally Correspondence to T. E.

show abstract

Protein disulfide isomerase: Multiple roles in the modification of nascent secretory proteins

Cited by 466 publications

References 18 publications

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Redox properties of protein disulfide isomerase (dsba) from escherichia coli

Localization of two interchain disulfide bridges in dimers of bovine α_s2‐casein

Contact Info

Product

Resources

About

Protein disulfide isomerase: Multiple roles in the modification of nascent secretory proteins

Cited by 466 publications

References 18 publications

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Redox properties of protein disulfide isomerase (dsba) from escherichia coli

Localization of two interchain disulfide bridges in dimers of bovine αs2‐casein

Contact Info

Product

Resources

About

Localization of two interchain disulfide bridges in dimers of bovine α_s2‐casein