Dual enzymatic properties of the cytoplasmic peptide: N-glycanase in C. elegans.
The endoplasmic reticulum-associated degradation (ERAD) of misfolded (glyco)proteins ensures that only functional, correctly folded proteins exit from the ER and that misfolded ones are degraded by the ubiquitin-proteasome system. During the degradation of misfolded glycoproteins, some of them are subjected to deglycosylation by the cytoplasmic peptide:N-glycanase (PNGase). The cytosolic PNGase is widely distributed throughout eukaryotes. Here we show that the nematode Caenorhabditis elegans PNG-1, the cytoplasmic PNGase orthologue in this organism, exhibits dual enzyme functions, not only as PNGase but also as an oxidoreductase (thioredoxin). Using an in vitro assay as well as an in vivo assay system in budding yeast, the N-terminal thioredoxin domain and the central transglutaminase domain were found to be essential for oxidoreductase activity and PNGase activity, respectively. Occurrence of a C. elegans mutation affecting a catalytic residue in the PNGase domain strongly suggests the functional importance of this protein in higher eukaryotes.
Suzuki
Tadashi
T
Department of Biochemistry, Osaka University Graduate School of Medicine, Japan. tsuzuki@biochem.med.osaka-u.ac.jp
Tanabe
Kaori
K
Hara
Izumi
I
Taniguchi
Naoyuki
N
Colavita
Antonio
A
D000818:Animals; D017173:Caenorhabditis elegans; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D051379:Mice; D009154:Mutation; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry
D006023:Glycoproteins; D013879:Thioredoxins; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase