RRC ID 5821
Author Stigliano ID, Caramelo JJ, Labriola CA, Parodi AJ, D'Alessio C.
Title Glucosidase II beta subunit modulates N-glycan trimming in fission yeasts and mammals.
Journal Mol Biol Cell
Abstract Glucosidase II (GII) plays a key role in glycoprotein biogenesis in the endoplasmic reticulum (ER). It is responsible for the sequential removal of the two innermost glucose residues from the glycan (Glc(3)Man(9)GlcNAc(2)) transferred to Asn residues in proteins. GII participates in the calnexin/calreticulin cycle; it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. GII is a heterodimer whose alpha subunit (GIIalpha) bears the glycosyl hydrolase active site, whereas its beta subunit (GIIbeta) role is controversial and has been reported to be involved in GIIalpha ER retention and folding. Here, we report that in the absence of GIIbeta, the catalytic subunit GIIalpha of the fission yeast Schizosaccharomyces pombe (an organism displaying a glycoprotein folding quality control mechanism similar to that occurring in mammalian cells) folds to an active conformation able to hydrolyze p-nitrophenyl alpha-d-glucopyranoside. However, the heterodimer is required to efficiently deglucosylate the physiological substrates Glc(2)Man(9)GlcNAc(2) (G2M9) and Glc(1)Man(9)GlcNAc(2) (G1M9). The interaction of the mannose 6-phosphate receptor homologous domain present in GIIbeta and mannoses in the B and/or C arms of the glycans mediates glycan hydrolysis enhancement. We present evidence that also in mammalian cells GIIbeta modulates G2M9 and G1M9 trimming.
Volume 20(17)
Pages 3974-84
Published 2009-9-1
DOI 10.1091/mbc.e09-04-0316
PII E09-04-0316
PMID 19605557
PMC PMC2735495
MeSH Amino Acid Sequence Animals Carbohydrate Conformation Carbohydrate Sequence Catalytic Domain Glucosides / metabolism Isoenzymes / chemistry Isoenzymes / genetics Isoenzymes / metabolism Molecular Sequence Data Mutagenesis Polysaccharides / metabolism* Protein Folding Protein Multimerization Protein Structure, Quaternary Protein Structure, Tertiary* Protein Subunits / chemistry* Protein Subunits / genetics Protein Subunits / metabolism* Rats Receptor, IGF Type 2 / genetics Receptor, IGF Type 2 / metabolism Schizosaccharomyces / enzymology Schizosaccharomyces pombe Proteins / chemistry* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Sequence Alignment alpha-Glucosidases / chemistry* alpha-Glucosidases / genetics alpha-Glucosidases / metabolism*
IF 3.791
Times Cited 44
DNA material S. pombe entry SpEnt26D11 (SPW010483) pDUAL-YFH1c (RDB06151) pREP1-ccdB2 (RDB06519).