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Pathways for protein disulphide bond formation.
A R Frand1, J W Cuozzo, C A Kaiser
1Dept of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Trends in Cell Biology
|April 8, 2000
Summary
Disulphide bond formation in the endoplasmic reticulum (ER) is crucial for secretory protein folding. New findings reveal glutathione oxidation competes with protein thiol oxidation in this pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Secretory protein folding relies on disulphide bond formation.
- The endoplasmic reticulum (ER) hosts a core pathway for these bonds.
- Eukaryotic disulphide bond formation involves Ero1p and protein disulphide isomerase (PDI).
Purpose of the Study:
- To outline the core pathway for disulphide bond formation in the ER.
- To investigate the role of Ero1p and PDI in oxidative folding.
- To explore the competition between glutathione and protein thiol oxidation.
Main Methods:
- Review of recent advances in genetics and cell biology.
- Analysis of the ER pathway for disulphide bond formation.
- Discussion of PDI homologues and prokaryotic systems.
Main Results:
- Oxidizing equivalents flow from Ero1p to secretory proteins via PDI.
- Glutathione oxidation in the ER competes with protein thiol oxidation, contrary to expectations.
- Contributions of PDI homologues to oxidative folding catalysis.
Conclusions:
- The ER pathway for disulphide bond formation is increasingly understood.
- Glutathione's role in ER redox balance is complex and competitive.
- Similarities exist between eukaryotic and prokaryotic disulphide-bond-forming systems.