LW012709

LW012709 - OGlycosylation Yeastmannoproteins dystroglycan...

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O-Glycosylation O-Glycosylation Ser/Thr GalNAc Mucins Ser/Thr Man Yeast mannoproteins α -dystroglycan Ser/Thr Fuc Notch Coagulation Factors Fibrinolytic Factors Ser/Thr GlcNAc Nuclear Proteins Cytoplasmic Proteins SEPARATE LECTURE Ser/Thr Glc Notch Thrombospondin Factor IX ALSO: Proteoglycans, Hydroxyproline/Hydroxylysine Glycosylation
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O-Glycosidic Linkage α Ser GalNAc O-glycosidic linkage is sensitive to alkali (regardless of stereochemistry) β -elimination O OH H H HO H O NAc H H OH NH 2 CH C H 2 C O GalNAc α
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Glycan synthesis in a cellular context Most O-Glycosylated proteins are synthesized in the secretory pathway
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O-Glycosylation O-Glycosylation Ser/Thr GalNAc Ser/Thr Man Ser/Thr Fuc Ser/Thr GlcNAc Ser/Thr Glc
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Mucin-Type O-GalNAc Glycans Major extracellular vertebrate O-glycan Begins in cis -Golgi by attachment of GalNAc in α - linkage to specific Ser/Thr residues Assembly is simpler than N- linked chains - no lipid intermediate is used Always involves nucleotide sugars Always occurs by addition to non-reducing terminus or by branching β 4 β 3 β 4 β 3 β 4 α 3 α 3 α 3 Ser/Thr β 3 β 6
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Polypeptide GalNAc Transferases >20 ppGalNAcT family members Share structural features in active site Some have lectin (ricin) domain Regions in white, pink, red, and black represent, respectively, 0–29%, 30–69%, 70– 99%, and 100% sequence identity (Hagen et al. (2003) Glycobiology 13:1R-16R).
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T (TF) Antigen Tn Antigen Core 2 GlcNAcT Core 1 GalT
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LW012709 - OGlycosylation Yeastmannoproteins dystroglycan...

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