scholarly journals Functional Differences in Yeast Protein Disulfide Isomerases

2001 ◽  
Vol 152 (3) ◽  
pp. 553-562 ◽  
Author(s):  
Per Nørgaard ◽  
Vibeke Westphal ◽  
Christine Tachibana ◽  
Lene Alsøe ◽  
Bjørn Holst ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Essential Gene ◽  
Carboxypeptidase Y ◽  
Gene Encoding ◽  
Disulfide Isomerase ◽  
Functional Differences ◽  
Disulfide Isomerases ◽  
Encoding Protein ◽  
Protein Disulfide ◽  
Catalyzed Oxidation

PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several cases, we found that the ability of the PDI1 homologues to restore viability to a pdi1-deleted strain when overexpressed was dependent on the presence of low endogenous levels of one or more of the other homologues. This shows that the homologues are not functionally interchangeable. In fact, Mpd1p was the only homologue capable of carrying out all the essential functions of Pdi1p. Furthermore, the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 (which contains two CXXS active site motifs). This underlines the essentiality of protein disulfide isomerase-catalyzed oxidation. Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. There are, however, no significant effects on ER-associated protein degradation in the various protein disulfide isomerase-deleted strains.

Functional differences between human and yeast protein disulfide isomerase family proteins

2004 ◽  
Vol 320 (2) ◽  
pp. 359-365 ◽  
Author(s):  
Taiji Kimura ◽  
Yasuhiro Hosoda ◽  
Yukiko Kitamura ◽  
Hideshi Nakamura ◽  
Tomohisa Horibe ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Yeast Protein ◽  
Disulfide Isomerase ◽  
Functional Differences ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

scholarly journals Nucleotide Sequence of a Wheat cDNA Encoding Protein Disulfide Isomerase

1995 ◽  
Vol 107 (1) ◽  
pp. 281-281 ◽  
Author(s):  
Y. Shimoni ◽  
G. Segal ◽  
Xz. Zhu ◽  
G. Galili
Keyword(s):  
Nucleotide Sequence ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Encoding Protein ◽  
Protein Disulfide

Molecular Cloning of a Fungal cDNA Encoding Protein Disulfide Isomerase

1994 ◽  
Vol 58 (8) ◽  
pp. 1424-1429 ◽  
Author(s):  
Tsutomu Kajino ◽  
Kiyoko Sarai ◽  
Takao Imaeda ◽  
Chie Idekoba ◽  
Osamu Asami ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Encoding Protein ◽  
Protein Disulfide

scholarly journals Protein Disulfide Isomerases Control the Secretion of Wnt proteins

2018 ◽  
Author(s):  
Nanna Torpe ◽  
Sandeep Gopal ◽  
Oguzhan Baltaci ◽  
Lorenzo Rella ◽  
Ava Handley ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Protein Disulfide Isomerase ◽  
Critical Role ◽  
Globular Structure ◽  
Disulfide Isomerase ◽  
Animal Development ◽  
Wnt Proteins ◽  
Protein Disulfide Isomerases ◽  
Disulfide Isomerases ◽  
Protein Disulfide

SummaryAppropriate Wnt morphogen secretion is required to control animal development and homeostasis. Although correct Wnt globular structure is essential for secretion, proteins that directly mediate Wnt folding and maturation are incompletely characterized. Here, we report that protein disulfide isomerase-1 (PDI-1), a protein folding catalyst and chaperone, controls secretion of the Caenorhabditis elegans Wnt ortholog EGL-20. We find that PDI-1 function is required to correctly form an anteroposterior EGL-20/Wnt gradient during embryonic development. Further, PDI-1 performs this role in EGL-20/Wnt-producing epidermal cells to cell-non-autonomously control EGL-20/Wnt-dependent neuronal migration. Using pharmacological inhibition, we further show that PDI function is required in human cells for Wnt3a secretion, revealing a conserved role for disulfide isomerases. Together, these results demonstrate a critical role for PDIs within Wnt-producing cells to control long-range developmental events that are dependent on Wnt secretion.

scholarly journals Active Site Mutations in Yeast Protein Disulfide Isomerase Cause Dithiothreitol Sensitivity and a Reduced Rate of Protein Folding in the Endoplasmic Reticulum

1997 ◽  
Vol 138 (6) ◽  
pp. 1229-1238 ◽  
Author(s):  
Bjørn Holst ◽  
Christine Tachibana ◽  
Jakob R. Winther
Keyword(s):  
Growth Rate ◽  
Active Site ◽  
Protein Disulfide Isomerase ◽  
Protein S ◽  
Optimal Growth ◽  
Carboxypeptidase Y ◽  
Oxidation Reactions ◽  
Disulfide Isomerase ◽  
Protein Disulfide

Aspects of protein disulfide isomerase (PDI) function have been studied in yeast in vivo. PDI contains two thioredoxin-like domains, a and a′, each of which contains an active-site CXXC motif. The relative importance of the two domains was analyzed by rendering each one inactive by mutation to SGAS. Such mutations had no significant effect on growth. The domains however, were not equivalent since the rate of folding of carboxypeptidase Y (CPY) in vivo was reduced by inactivation of the a domain but not the a′ domain. To investigate the relevance of PDI redox potential, the G and H positions of each CGHC active site were randomly mutagenized. The resulting mutant PDIs were ranked by their growth phenotype on medium containing increasing concentrations of DTT. The rate of CPY folding in the mutants showed the same ranking as the DTT sensitivity, suggesting that the oxidative power of PDI is an important factor in folding in vivo. Mutants with a PDI that cannot perform oxidation reactions on its own (CGHS) had a strongly reduced growth rate. The growth rates, however, did not correlate with CPY folding, suggesting that the protein(s) required for optimal growth are dependent on PDI for oxidation. pdi1-deleted strains overexpressing the yeast PDI homologue EUG1 are viable. Exchanging the wild-type Eug1p C(L/I)HS active site sequences for C(L/I)HC increased the growth rate significantly, however, further highlighting the importance of the oxidizing function for optimal growth.

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