ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing
P Maattanen1, G Kozlov, K Gehring
1Biochemistry Department, McGill University, 3655 Promenade Sir William Osler, Montréal, QC H3G 1Y6, Canada. veli-pekka.maatanen@po-box.mcgill.ca
Abstract:
Secretory proteins become folded and acquire stabilizing disulfide bonds in the endoplasmic reticulum (ER). Correct disulfide bond formation is a key step in ER quality control (ERQC). Proteins with incorrect disulfide bonds are recognized by the quality control machinery and are retrotranslocated into the cytosol where they are degraded by the proteasome. The mammalian ER contains 17 disulfide isomerases and at least one of them, ERp57, works in conjunction with the ER lectin-like chaperones calnexin and calreticulin. The targeting of ERp57 to calnexin-calreticulin is mediated by its noncatalytic b' domain, and analogous domains in other disulfide isomerases likely determine their substrate and partner preferences. This review discusses some explanations for the multiplicity of disulfide isomerases and highlights structural differences in the b' domains of PDI and ERp57 as an example of how noncatalytic domains define specialized roles in oxidative folding.
Related Concept Videos
Protein Modifications in the RER
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Intrinsically Disordered Proteins
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Protein-protein Interfaces
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...


