‘Something in the way she moves’: The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)

Abstract

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI.

Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities

“…For example, PDI is nitrosylated in brains of AD and PD patients, which causes improper folding of toxic proteins (512). PDI is a chaperone enzyme present in the ER that modulates formation of disulfide bonds during their synthesis and maturation (162,186). In neurodegenerative disorders and during ischemia, accumulation of denatured proteins causes ER dysfunction.…”

Disulfide isomerase ERp57 improves the stability and immunogenicity of H3N2 influenza virus hemagglutinin

“…In order to improve influenza vaccines, many efforts have been made to stabilize the expressed HA proteins, such as fusing HA extracellular domain to the trimerization sequences or introducing a CFLLC minidomain into the transmembrane domain of HA proteins [16,18,20,34,[39][40][41]. PDIs, one of the most important protein families in cells, catalyze the formation of intra-and inter-molecular disulfide bonds between cysteines and help the correct folding of proteins [24][25][26]. ERp57 has been proved to play a crucial role in the post-transcription of HA proteins [30].…”

“…PDIs are a kind of enzyme that catalyzes redox reaction in the endoplasmic reticulum (ER), which can help the formation of disulfide bonds between cysteines and the correct folding of proteins [24][25][26]. There are more than 20 members of this protein family in mammals [23,27].…”

Weighted Gene Co-expression Network Analysis Identifies Critical Genes for the Production of Cellulase and Xylanase in Penicillium oxalicum

“…The remaining 63 genes of 120 members in module MEivory included three genes (POX05586, POX01637, and POX07741) involved in metabolism, three genes (POX03367, POX07086, and POX07745) involved in genetic information processing, one gene (POX01689) involved in environmental information processing, and 56 unknown genes, through the annotation using KEGG database. POX03367 encoding putative ATP-dependent Clp protease POX03367/ClpX, and POX07086 and POX07745 encoding disulfide-isomerases were reported to be associated with protein homeostasis (Freedman et al, 2017;Bell et al, 2018). Moreover, protein POX01689 shared 62.0% identity with Ras GTase Rsr1 (accession number CAA59809.1), which is involved in the regulation of cell polarity in Saccharomyces cerevisiae (Miller et al, 2019).…”