Protein folding PDI displays
oxidoreductase and
isomerase properties, both of which depend on the type of substrate that binds to protein disulfide-isomerase and changes in protein disulfide-isomerase's redox state.
Regular oxidative folding mechanism and pathway PDI is specifically responsible for folding proteins in the ER. For the reductase method, a misfolded substrate disulfide bond is converted to a pair of reduced cysteine residues by the transfer of electrons from glutathione and NADPH. Afterwards, normal folding occurs with oxidative disulfide bond formation between the correct pairs of substrate cysteine residues, leading to a properly folded protein. For the isomerase method, intramolecular rearrangement of substrate functional groups is catalyzed near the
N terminus of each active site.
Other functions Immune system Protein disulfide-isomerase helps load
antigenic peptides into
MHC class I molecules. These molecules (MHC I) are related to the peptide presentation by
antigen-presenting cells in the
immune response. Protein disulfide-isomerase has been found to be involved in the breaking of bonds on the
HIV gp120 protein during HIV infection of
CD4 positive cells, and is required for HIV infection of
lymphocytes and monocytes. Some studies have shown it to be available for HIV infection on the surface of the cell clustered around the CD4 protein. Yet conflicting studies have shown that it is not available on the cell surface, but instead is found in significant amounts in the blood plasma.
Chaperone activity Another major function of protein disulfide-isomerase relates to its activity as a
chaperone; its b' domain aids in the binding of
misfolded protein for subsequent
degradation. They respond to high levels of misfolded proteins in the ER through intracellular signaling cascades that can activate PDI's chaperone activity. These signals can also inactivate translation of these misfolded proteins, because the cascade travels from the ER to the nucleus. == Activity assays ==