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PMID:19279007

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Citation

Sakoh-Nakatogawa, M, Nishikawa, S and Endo, T (2009) Roles of protein-disulfide isomerase-mediated disulfide bond formation of yeast Mnl1p in endoplasmic reticulum-associated degradation. J. Biol. Chem. 284:11815-25

Abstract

The endoplasmic reticulum (ER) has a strict protein quality control system. Misfolded proteins generated in the ER are degraded by the ER-associated degradation (ERAD). Yeast Mnl1p consists of an N-terminal mannosidase homology domain and a less conserved C-terminal domain and facilitates the ERAD of glycoproteins. We found that Mnl1p is an ER luminal protein with a cleavable signal sequence and stably interacts with a protein-disulfide isomerase (PDI). Analyses of a series of Mnl1p mutants revealed that interactions between the C-terminal domain of Mnl1p and PDI, which include an intermolecular disulfide bond, are essential for subsequent introduction of a disulfide bond into the mannosidase homology domain of Mnl1p by PDI. This disulfide bond is essential for the ERAD activity of Mnl1p and in turn stabilizes the prolonged association of PDI with Mnl1p. Close interdependence between Mnl1p and PDI suggests that these two proteins form a functional unit in the ERAD pathway.

Links

PubMed PMC2673250 Online version:10.1074/jbc.M900813200

Keywords

Disulfides/metabolism; Endoplasmic Reticulum/enzymology; Endoplasmic Reticulum/genetics; Enzyme Stability/physiology; Glycoproteins/genetics; Glycoproteins/metabolism; Mannosidases/genetics; Mannosidases/metabolism; Protein Disulfide-Isomerases/genetics; Protein Disulfide-Isomerases/metabolism; Protein Folding; Protein Sorting Signals/physiology; Protein Structure, Tertiary/physiology; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:MNL1

located_in

GO:0005788: endoplasmic reticulum lumen

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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