Protein disulfide isomerase: The multifunctional redox chaperone of the endoplasmic reticulum

Noiva, Robert

doi:10.1006/scdb.1999.0319

Cited by 262 publications

(220 citation statements)

References 104 publications

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“…Fragment 441-491 and the Abnormal Behavior of PDI on SEC-In contrast to the a, b, bЈ, and aЈ domains, the C-terminal sequence 463-491, c, has never been assigned as a structural domain but is just an extension (2), probably with no secondary or tertiary structure (38). We prepared several PDI mutants with the C-terminal sequence deleted to different extents in order to examine the behavior of these mutants by SEC.…”

Section: Saxs Parameters-as Shown Inmentioning

confidence: 99%

Annular Arrangement and Collaborative Actions of Four Domains of Protein-disulfide Isomerase

Hong

Shi

et al. 2006

Journal of Biological Chemistry

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We presented for the first time a small angle x-ray scattering study of intact protein-disulfide isomerase (PDI) in solution. The restored model revealed that PDI is a short and roughly elliptical cylinder with a molecular mass of 69 kDa and dimensions of 105 ؋ 65 ؋ 40 Å , and the four thioredoxin-fold domains in the order a-bb-a are arranged in an annular fashion. Atomic force microscope imaging also supported the finding that PDI appears as an approximately flat elliptical cylinder. A PDI species with apparent molecular mass of 116 kDa measured by using size-exclusion chromatography, previously assumed to be a dimer, was determined to exist mainly as a monomer by using analytical ultracentrifugation. The C-terminal fragment 441-491 contributed to the anomalous molecular mass determination of PDI by size-exclusion chromatography. The annular model of PDI accounted for the cooperative properties of the four domains in both the isomerase and chaperone functions of PDI.Protein-disulfide isomerase (PDI, 3 EC 5.3.4.1) is an abundant multifunctional protein within the lumen of the endoplasmic reticulum (1, 2). It plays important roles in many physiological processes as both an enzyme and a molecular chaperone (3-5) by assisting in folding, unfolding, and translocation of many disulfide-containing proteins (6) and even some disulfide-free proteins (7). In addition, PDI serves as an obligatory ␤ subunit of hetero-oligomeric prolyl 4-hydroxylase (8) and microsomal triglyceride transfer protein (9) to maintain highly insoluble ␣ subunits in an active, nonaggregated conformation (10).The four-domain architecture of PDI in the order a-b-bЈ-aЈ was proposed when the PDI cDNA was first sequenced, according to the internal sequence homology within the molecule (11). Later, the domain boundaries were defined (12) and further refined as shown in Scheme 1 by combined use of protein engineering, limited proteolysis, and bioinformatics (13-16). The a and aЈ domains, each with a -CGHC-motif as the active site, share 47% sequence identity, whereas the b and bЈ domains, with no such active site motif, share 28% sequence identity (11). The C-terminal 29 residues, 463-491, constitute an acidic c extension (2), in which over half of the residues are Glu/Asp, and represent a putative Ca 2ϩ -binding region (12). The three-dimensional structure determined by using NMR of the a domain, which shares 27% identity to thiroredoxin (Trx), shows a Trx-fold (15), and the b domain, which shows no significant sequence similarity to the a and Trx, also has a Trx-fold (14). PDI has thus been suggested to consist of four Trx-fold domains (14). Recently, a 19-amino acid linker region, 333-351, was identified between the bЈ and aЈ domains (16), which was suggested to potentially allow more flexibility between these domains than between the other domains. The three-dimensional structure of the entire PDI molecule, or of any other catalytically active eukaryotic PDI family member, has not yet been determined even though PDI was discovered over 40 years ago....

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Section: Saxs Parameters-as Shown Inmentioning

confidence: 99%

Annular Arrangement and Collaborative Actions of Four Domains of Protein-disulfide Isomerase

Hong

Shi

et al. 2006

Journal of Biological Chemistry

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“…Other ER resident proteins like protein disulfide isomerase and related molecules, are involved in folding of nascent polypeptides and the isomerization of disulfide bridges (Noiva and Lennarz 1992). This function is mediated by a thioredoxin-like catalytic domain that contains the motif [Cys-X-X-Cys] (Noiva and Lennarz 1992, Chivers et al 1996).…”

Section: The Wind Gene Encodes An Endoplasmic Reticulum Proteinmentioning

confidence: 99%

windbeutel,a gene required for dorsoventral patterning inDrosophila,encodes a protein that has homologies to vertebrate proteins of the endoplasmic reticulum

Konsolaki

Schüpbach

1998

Genes Dev.

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The formation of the dorsoventral axis of the Drosophila embryo depends on cell-cell interactions that take place in the female ovary and involve the activation of transmembrane receptors by secreted ligands. The gene windbeutel functions in the somatic follicle cells of the ovary and is required for the generation of a signal that will determine the ventral side of the embryo. This signal originates in the follicle cells during oogenesis, but its actions are only manifested after fertilization, when the egg has already been laid. We have performed a molecular analysis of windbeutel. We have found that windbeutel encodes a putative resident protein of the endoplasmic reticulum, and has homologs in rats and humans. The gene is expressed for a brief period of time in the follicle cells of the ovary, at around the time when the dorsoventral axis of the egg chamber is first established. We propose that Windbeutel is responsible for the folding and/or modification of a specific factor that is secreted from the follicle cells and participates in the activation of the ventralizing signal.

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“…PDI, a member of the thioldisulfide oxidoreductase family, displays thiol isomerase, oxidase, and reductase activity. The canonical function of PDI is a disulfide bond formation in the nascent protein and protein folding in the endoplasmic reticulum (11). PDI has multiple biological functions and interacts with numerous proteins (12).…”

mentioning

confidence: 99%

Protein Disulfide Isomerase Directly Interacts with β-Actin Cys374 and Regulates Cytoskeleton Reorganization

Sobierajska

Skurzynski

Stasiak

et al. 2014

Journal of Biological Chemistry

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Background: PDI regulates cytoskeleton reorganization by the thiol-disulfide exchange in ␤-actin. Results: PDI directly binds to Cys 374 of ␤-actin during cell adhesion and spreading. Conclusion: Interaction of PDI with ␤-actin is induced by integrin-mediated cell adhesion and promotes cytoskeleton reorganization. Significance: PDI is a new regulator of the intramolecular disulfide-thiol rearrangement of ␤-actin in response to ␣IIb␤3 integrin engagement.

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Protein disulfide isomerase: The multifunctional redox chaperone of the endoplasmic reticulum

Cited by 262 publications

References 104 publications

Annular Arrangement and Collaborative Actions of Four Domains of Protein-disulfide Isomerase

Annular Arrangement and Collaborative Actions of Four Domains of Protein-disulfide Isomerase

windbeutel,a gene required for dorsoventral patterning inDrosophila,encodes a protein that has homologies to vertebrate proteins of the endoplasmic reticulum

Protein Disulfide Isomerase Directly Interacts with β-Actin Cys374 and Regulates Cytoskeleton Reorganization

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