ER Oxidoreductin
Encyclopedia
ER oxidoreductin 1 is an oxidoreductase enzyme
that catalyses the formation and isomerization of protein disulfide bonds in the endoplasmic reticulum
(ER) of eukaryotes. ER Oxidoreductin 1 (Ero1) is a conserved, luminal, glycoprotein
that is tightly associated with the ER membrane, and is essential for the oxidation of protein dithiols. Since disulfide bond formation is an oxidative process, the major pathway of its catalysis has evolved to utilise oxidoreductase
s, which become reduced during the thiol-disulfide exchange reactions that oxidise the cysteine thiol
groups of nascent polypeptides. Ero1 is required for the introduction of oxidising equivalents into the ER and their direct transfer to protein disulfide isomerase
(PDI), thereby ensuring the correct folding and assembly of proteins that contain disulfide bonds in their native state.
Homologues of the Saccharomyces cerevisiae
Ero1 proteins have been found in all eukaryotic organisms examined, and contain seven cysteine
residues that are absolutely conserved, including three that form the sequence Cys–X–X–Cys–X–X–Cys (where X can be any residue).
atoms of a disulfide bond in the oxidised partner, by a thiolate anion derived from a reactive cysteine in a reduced partner. This generates mixed disulfide intermediates, and is followed by a second, this time intramolecular, nucleophilic attack by the remaining thiolate anion in the formerly reduced partner, to liberate both oxidoreductases. The balance of evidence discussed thus far supports a model in which oxidising equivalents are sequentially transferred from Ero1 via a thiol–disulfide exchange reaction to PDI, with PDI then undergoing a thiol–disulfide exchange with the nascent polypeptide, thereby enabling the formation of disulfide bonds within the nascent polypeptide.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyses the formation and isomerization of protein disulfide bonds in the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
(ER) of eukaryotes. ER Oxidoreductin 1 (Ero1) is a conserved, luminal, glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
that is tightly associated with the ER membrane, and is essential for the oxidation of protein dithiols. Since disulfide bond formation is an oxidative process, the major pathway of its catalysis has evolved to utilise oxidoreductase
Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
s, which become reduced during the thiol-disulfide exchange reactions that oxidise the cysteine thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
groups of nascent polypeptides. Ero1 is required for the introduction of oxidising equivalents into the ER and their direct transfer to protein disulfide isomerase
Protein disulfide isomerase
Protein disulfide isomerase or PDI is an enzyme in the endoplasmic reticulum in eukaryotes that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold...
(PDI), thereby ensuring the correct folding and assembly of proteins that contain disulfide bonds in their native state.
Homologues of the Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
Ero1 proteins have been found in all eukaryotic organisms examined, and contain seven cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues that are absolutely conserved, including three that form the sequence Cys–X–X–Cys–X–X–Cys (where X can be any residue).
The mechanism of thiol–disulfide exchange between oxidoreductases
The mechanism of thiol–disulfide exchange between oxidoreductases is understood to begin with the nucleophilic attack on the sulfurSulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
atoms of a disulfide bond in the oxidised partner, by a thiolate anion derived from a reactive cysteine in a reduced partner. This generates mixed disulfide intermediates, and is followed by a second, this time intramolecular, nucleophilic attack by the remaining thiolate anion in the formerly reduced partner, to liberate both oxidoreductases. The balance of evidence discussed thus far supports a model in which oxidising equivalents are sequentially transferred from Ero1 via a thiol–disulfide exchange reaction to PDI, with PDI then undergoing a thiol–disulfide exchange with the nascent polypeptide, thereby enabling the formation of disulfide bonds within the nascent polypeptide.