ArticleThe Journal of biological chemistry2009
Generating an unfoldase from thioredoxin-like domains.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Unveiling the thioredoxin fold: a systematic review and bioinformatic analysis of protein disulfide isomerase and Dsb family proteins.Frontiers in bioinformatics · 2026Pooled it
- Protein disulfide isomerase does not act as an unfoldase in the disassembly of cholera toxin.Bioscience reports · 2018Article
- Intracellular trafficking of bacterial toxins.Current opinion in cell biology · 2016Review
- PDI reductase acts on Akita mutant proinsulin to initiate retrotranslocation along the Hrd1/Sel1L-p97 axis.Molecular biology of the cell · 2015Article
- The nucleotide exchange factors Grp170 and Sil1 induce cholera toxin release from BiP to enable retrotranslocation.Molecular biology of the cell · 2015Article
- On the role of protein disulfide isomerase in the retrograde cell transport of secreted phospholipases A2.PloS one · 2015Article
- How viruses use the endoplasmic reticulum for entry, replication, and assembly.Cold Spring Harbor perspectives in biology · 2013Review
- Endoplasmic reticulum-dependent redox reactions control endoplasmic reticulum-associated degradation and pathogen entry.Antioxidants & redox signaling · 2012Review
- The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology.Physiological reviews · 2012Review
- Disordered form of the scaffold protein IscU is the substrate for iron-sulfur cluster assembly on cysteine desulfurase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a'.The Journal of biological chemistry · 2012Article
- Protein-disulfide isomerase displaces the cholera toxin A1 subunit from the holotoxin without unfolding the A1 subunit.The Journal of biological chemistry · 2011Article
- A PDI family network acts distinctly and coordinately with ERp29 to facilitate polyomavirus infection.Journal of virology · 2011Article
- Protein disulfide isomerase isomerizes non-native disulfide bonds in human proinsulin independent of its peptide-binding activity.Protein science : a publication of the Protein Society · 2011Article
- Plasticity of human protein disulfide isomerase: evidence for mobility around the X-linker region and its functional significance.The Journal of biological chemistry · 2010Article
- The Ero1alpha-PDI redox cycle regulates retro-translocation of cholera toxin.Molecular biology of the cell · 2010Article
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-disulfide isomerase (PDI), an endoplasmic reticulum (ER)-resident protein, is primarily known as a catalyst of oxidative protein folding but also has a protein unfolding activity. We showed previously that PDI unfolds the cholera toxin A1 (CTA1) polypeptide to facilitate the ER-to-cytosol retrotranslocation of the toxin during intoxication. We now provide insight into the mechanism of this unfoldase activity. PDI includes two redox-active (a and a') and two redox-inactive (b and b') thioredoxin-like domains, a linker (x), and a C-terminal domain (c) arranged as abb'xa'c. Using recombinant PDI fragments, we show that binding of CTA1 by the continuous PDIbb'xa' fragment is necessary and sufficient to trigger unfolding. The specific linear arrangement of bb'xa' and the type a domain (a' versus a) C-terminal to bb'x are additional determinants of activity. These data suggest a general mechanism for the unfoldase activity of PDI: the concurrent and specific binding of bb'xa' to particular regions along the CTA1 molecule triggers its unfolding. Furthermore, we show the bb' domains of PDI are indispensable to the unfolding reaction, whereas the function of its a' domain can be substituted partially by the a' domain from ERp57 (abb'xa'c) or ERp72 (ca degrees abb'xa'), PDI-like proteins that do not unfold CTA1 normally. However, the bb' domains of PDI were insufficient to convert full-length ERp57 into an unfoldase because the a domain of ERp57 inhibited toxin binding. Thus, we propose that generating an unfoldase from thioredoxin-like domains requires the bb'(x) domains of PDI followed by an a' domain but not preceded by an inhibitory a domain.
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