Abstract
Protein Disulfide Isomerase (PDI) was originally discovered fifty years ago as the first protein folding catalyst and isolated from rat liver [1]. It was demonstrated early on that PDI acts as a dithiol–disulfide oxidoreductase capable of reducing, oxidizing and isomerizing disulfide bonds. Independently of its redox activity, PDI can also act as a vital cellular defense against the intracellular accumulation of misfolded proteins via its chaperone activity [2].
Highlights
Protein Disulfide Isomerase (PDI) was originally discovered fifty years ago as the first protein folding catalyst and isolated from rat liver [1]
Cell adhesion molecules (CAMs) including integrins and selectins control the process of leukocyte trafficking to sites of infection or injury by facilitating cell rolling and transmigration through endothelial cells
The expression of protein disulfide isomerase (PDI) on the surface of several cell types including leukocytes have been demonstrated, suggesting an enzymatic mediator function for disulfide exchange in the cell-surface receptors which might play a role in the integrin’s ligand-induced conformational change which is instrumental for the integrin αMb2 (CD11b/CD18) to efficiently adhere to the vascular endothelium during the recruitment of leukocyte to an inflammatory site [6]
Summary
Of its redox activity, PDI can act as a vital cellular defense against the intracellular accumulation of misfolded proteins via its chaperone activity [2]. Most PDI family members share in common catalytic and noncatalytic thioredoxin-like domains. The and a’ domains contain catalytic CXXC motifs reacting with thiol groups in substrate proteins. PDIs are considered to be primarily ER resident proteins, several other cellular locations have been reported for these proteins including the cell surface, cytosol, mitochondria, and extracellular matrix [4]. The key roles played by these proteins in cell adhesion and inflammation, cardiovascular diseases, cancer and host-pathogen interaction suggest the potential use of PDI as novel therapeutic targets, which will be discussed in this review
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