Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties.
Oligosaccharyltransferase (OST) is an integral membrane protein that catalyzes N-linked glycosylation of nascent proteins in the lumen of the endoplasmic reticulum. Although the yeast OST is an octamer assembled from nonhomologous subunits (Ost1p, Ost2p, Ost3p/Ost6p, Ost4p, Ost5p, Wbp1p, Swp1p, and Stt3p), the composition of the vertebrate OST was less well defined. The roles of specific OST subunits remained enigmatic. Here we show that genomes of most multicellular eukaryotes encode two homologs of Stt3p and mammals express two homologs of Ost3p. The Stt3p and Ost3p homologs are assembled together with the previously described mammalian OST subunits (ribophorins I and II, OST48, and DAD1) into complexes that differ significantly in enzymatic activity. Tissue and cell type-specific differences in expression of the Stt3p homologs suggest that the enzymatic properties of oligosaccharyltransferase are regulated in eukaryotes to respond to alterations in glycoprotein flux through the secretory pathway and may contribute to tissue-specific glycan heterogeneity.
Kelleher
Daniel J
DJ
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, USA.
Karaoglu
Denise
D
Mandon
Elisabet C
EC
Gilmore
Reid
R
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D005057:Eukaryotic Cells / Q000201:enzymology*; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism; D006602:Hexosyltransferases; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011134:Polysaccharides / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000302:isolation & purification*; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D014166:Transferases / Q000235:genetics / Q000302:isolation & purification*
D006023:Glycoproteins; D008565:Membrane Proteins; D011134:Polysaccharides; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D014166:Transferases; D006602:Hexosyltransferases; C096554:STT3 protein, S cerevisiae; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase