Functional differences in yeast protein disulfide isomerases
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Functional differences in yeast protein disulfide isomerases. / Nørgaard, Per; Westphal, Vibeke; Tachibana, Christine; Alsøe, Lene; Holst, Bjørn; Winther, Jakob R.
I: Journal of Cell Biology, Bind 152, Nr. 3, 2001, s. 553-562.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Functional differences in yeast protein disulfide isomerases
AU - Nørgaard, Per
AU - Westphal, Vibeke
AU - Tachibana, Christine
AU - Alsøe, Lene
AU - Holst, Bjørn
AU - Winther, Jakob R.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Blotting, Western
KW - Dithiothreitol
KW - Endoplasmic Reticulum
KW - Escherichia coli
KW - Gene Deletion
KW - Genes, Essential
KW - Genes, Fungal
KW - Glycosylation
KW - Mutation
KW - Plasmids
KW - Precipitin Tests
KW - Protein Disulfide-Isomerases
KW - Protein Folding
KW - Saccharomyces cerevisiae
U2 - 10.1083/jcb.152.3.553
DO - 10.1083/jcb.152.3.553
M3 - Journal article
C2 - 11157982
VL - 152
SP - 553
EP - 562
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 3
ER -
ID: 43973835