Introduction ERp18
The endoplasmic reticulum (ER) is found in eukaryotic cells and is essential for correct folding and maturation of proteins targeted for cell secretion or destined for plasma membranes[1]. Correct native disulfide bond formation is vital for protein maturation[2]. Within the Endoplasmic reticulum a number of enzymatic proteins work together to ensure the correct disulfide bonding of the proteins. Overall, the protein activity within the ER is known about, however the individual roles of the proteins remains very much a mystery[2].
Disulfide bond formation is a complex process and occurs along a number of different pathways. In each pathway there is a number of stages to be considered[2]. These include:
I. Oxidation – the formation of disulfide bonds[3];
II. Reduction – the breaking of incorrect disulfide bonds[3]; and
III. Isomerisation – the rearrangement of existing disulfide bonds[3].
The most common mechanism of bond formation involves the exchange of free thiols with disulfide bonded molecules. This is catalysed by a group of proteins called thiol - disulfide oxidoreductases. The activity of thiol – disulfide oxidoreductases depends largely on a CXXC motif[1].
The most commonly studied thiol - disulfide oxdireductase is the Protien Disulfide Isomerase (PDI). [1] “PDI catalyses the formation, reshuffling, or reduction of disulfide bonds in a manner dependent on the redox environment and the characteristics of the substrate protein.”[1]
The novel protein ERp18 is suggested to be a thiol – disulfide oxidoreductase, similar to the PDI family, involved more so in the formation of disulfide bonds than in the reduction of these bonds [1, 3].
ERp18 is a 172 amino acid residue, 18kD protein, located within the endoplasmic reticulum. It is often referred to as ERp19 or ERp16. ERp16 is the mature protein, consisting of 146 amino acid residues and is 16kD in size.
References
1. Jeong, W., et al., ERp16, an Endoplasmic Reticulum-resident Thiol-disulfide Oxidoreductase
BIOCHEMICAL PROPERTIES AND ROLE IN APOPTOSIS INDUCED BY ENDOPLASMIC RETICULUM STRESS. J. Biol. Chem, 2008. 283(37): p. 25557-25566.
2. Alanen, H.I., et al., Functional Characterization of ERp18, a New Endoplasmic Reticulum-located Thioredoxin Superfamily Member. J. Biol. Chem, 2003. 278(31): p. 28912-28920.
3. Ellgaard, L. and L.W. Ruddock, The human protein disulphide isomerase family: substrate interactions and functional properties EMBO reports 2005. 6(1): p. 28-32.
