1 / 28

Synthesis and Structure of Major Glycan Classes

Synthesis and Structure of Major Glycan Classes. 1/24/05. Large O-linked Glycosaminoglycans and poly-lactosamine structures Glycoprotein N-linked and O-linked oligosaccharides Glycolipid oligosaccharides. Symbolic Representation. Simplified Traditional. The building blocks.

asalvatore
Download Presentation

Synthesis and Structure of Major Glycan Classes

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Synthesis and Structure of Major Glycan Classes 1/24/05

  2. Large O-linked Glycosaminoglycans and poly-lactosamine structures • Glycoprotein N-linked and O-linked oligosaccharides • Glycolipid oligosaccharides

  3. Symbolic Representation Simplified Traditional The building blocks

  4. Glycan synthesis in a cellular context

  5. Overview From ER through Trans-Golgi and points inbetween

  6. ER processing of N-linked glycans

  7. “Hybrid” Major Classes of N-Glycans “Complex” “High-Mannose” (oligo-mannose)

  8. GlcNAc Man Glc Gal Sia Fuc Dolichol Biosynthesis of N-Glycans:Production of GlcNAc-P-P-Dolichol Tunicamycin Blocks - not very specific! Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  9. GlcNAc Man Glc Gal Sia Fuc Biosynthesis of the N-GlycanPrecursor on the Cytosolic Leaflet of the Endoplasmic Reticulum (ER) CDG = Congenital Disorder of Glycosylation in Humans Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  10. GlcNAc Man Glc Gal Sia Fuc Biosynthesis of the N-GlycanPrecursor on Lumenal Leaflet of ER Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  11. GlcNAc Man Glc Gal Sia Fuc Completion of Biosynthesis of N-GlycanPrecursor on Lumenal Leaflet of ER- and Transfer to Protein Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  12. Target “sequon” for N-glycosylation • Necessary but not sufficient • X = any amino acid except proline • Rarely can be Asn-X-Cys • Transfer co-translational/immediate • post-translational before folding • ~2/3 of proteins have sequons • ~ 2/3 sequons actually occupied • (some variably) Yeast OST complex contains nine membrane-bound subunits Oligosaccharyltransferase complex (OST) in the ER membrane transfers the dolichol N-glycan precursor to asparagine residues on nascently translated proteins

  13. GlcNAc Man Glc Gal Sia Fuc Initial Processing of N-Glycans in the ER and Golgi ER Golgi Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  14. Improperly folded proteins are re-glucosylated by glucosyltransferase which acts as “sensor” for improper folding 3 Glucose Residues Calnexin (and Calcireticulin) function during glycoprotein folding in the endoplasmic reticulum

  15. ER glycolipid synthesis

  16. Biosynthesis of Ceramide and Glucosylceramide

  17. ER glycolipid synthesis

  18. Basic Glycosylphosphatidylinositol (GPI) Anchor Phospholipid

  19. Cell surface hydrolases Protozoal antigens alkaline phosphatase trypanosome VSG acetylcholinesterase leishmanial protease 5’ nucleotidase plasmodium antigens Adhesion molecules Mammalian antigens neural cell adhesion molecule carcinoembryonic antigen heparan sulfate proteoglycan Thy-1 Others scrapie prion protein folate receptor decay accelerating factor Examples of GPI-Anchored Proteins

  20. Structure of the Basic GPI Anchor

  21. Structural Analysis of the GPI AnchorEnzymatic and chemical cleavage sites are useful in identifying GPI anchored membrane proteins

  22. Examples of C-Terminal Sequences Signaling the Addition of GPI-Anchors Bold AA is site of GPI attachment Sequence to right is cleaved by the transpeptidase upon Anchor addition

  23. Golgi processing of N-linked glycans

  24. GlcNAc Man Glc Gal Sia Fuc Completion of Processing of N-Glycans in ER and Golgi Final products often show “microheterogeneity” at each N-Glycosylation site Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79

  25. GlcNAc-Transferases Determine Number of“Antennae” of N-glycans

  26. Some representative examples of mammalian complex-type N-glycans

  27. Slime Yeast Plants Mold Insects 3 a a3 6a a3 6a a 4 N N Asn Asn a 4 b 2 a 4 a3 a6 N N Vertebrates Asn Asn Evolutionary Variations of the N-glycan Processing Pathway “Pauci- mannose”

  28. Golgi processing of O-linked glycans

More Related