The protein disulphide-isomerase family: unravelling a string of folds

Abstract

The mammalian protein disulphide-isomerase (PDI) family encompasses several highly divergent proteins that are involved in the processing and maturation of secretory proteins in the endoplasmic reticulum. These proteins are characterized by the presence of one or more domains of roughly 95-110 amino acids related to the cytoplasmic protein thioredoxin. All but the PDI-D subfamily are composed entirely of repeats of such domains, with at least one domain containing and one domain lacking a redox-active -Cys-Xaa-Xaa-Cys-tetrapeptide. In addition to their known roles as redox catalysts and isomerases, the last few years have revealed additional functions of the PDI proteins,

Protein Disulfide Isomerase-2 of Arabidopsis Mediates Protein Folding and Localizes to Both the Secretory Pathway and Nucleus, Where It Interacts with Maternal Effect Embryo Arrest Factor

“…PDI utilizes the thioredoxin domains for catalysis, which places them in the superfamily of thioredoxin-like proteins (Motohashi et al, 2001). However, PDIs are several-fold larger than thioredoxins (Ferrari and Soling, 1999;Lu and Christopher, 2008) and have other functions in addition to protein folding.…”

“…In animals and yeast, PDIs act as chaperones by preventing proteins from aggregating (Ferrari and Soling, 1999;Lamberg et al, 1996;Lumb and Bulleid, 2002) and are key subunits in numeous enzyme complexes (John and Bulleid, 1994;Lamberg et al, 1996). PDIs are required for cell viability (Ferrari and Soling, 1999) and differentiation (Ohtani et al, 1993), ion uptake (Honscha et al, 1993), regulating transcription (Markus and Benezra, 1999) and are found in the nucleus, cytoplasm, ER, mitochondria, and extracellular milieu (Couet et al, 1996;Lahav et al, 2000;Rigobello et al, 2001;Turano et al, 2002;Wilson et al, 1998).…”

“…PDIs are required for cell viability (Ferrari and Soling, 1999) and differentiation (Ohtani et al, 1993), ion uptake (Honscha et al, 1993), regulating transcription (Markus and Benezra, 1999) and are found in the nucleus, cytoplasm, ER, mitochondria, and extracellular milieu (Couet et al, 1996;Lahav et al, 2000;Rigobello et al, 2001;Turano et al, 2002;Wilson et al, 1998). Recently, human PDI was found to bind signal peptide peptidase and unfold target proteins, leading to their dislocation from the ER to the cytoplasm and degradation by the ubiquitin-proteasome system, which is a process known as ER-associated degradation (ERAD) (Lee et al, 2010).…”

Phage display identifies thioredoxin and superoxide dismutase as novel protein kinase C-interacting proteins: thioredoxin inhibits protein kinase C-mediated phosphorylation of histone

“…Thioredoxin is a 12 kDa protein that has oxidoreductase activity via its S # -(SH) # active site [15]. Oxidized thioredoxin is reduced by an NADPH-dependent thioredoxin reductase.…”

Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity

“…ER60 (Erp60), also called Erp57, is a protein disulphide isomerase precursor, a human glucose-regulated protein and the closest-known homologue of PDI (Frickel et al, 2004) sharing 33% of the same amino acids as PDI. ER60 is expressed in response to conditions of stress (Ferrari and Soling, 1999). ER60 was found to show a two-fold upregulation in response to Gefitinib compared with untreated and DMSOtreated A431 cells conditioned medium.…”