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Evolution of Glycan Diversity and Cellular Organization of Glycosylation

Evolution of Glycan Diversity and Cellular Organization of Glycosylation. Sarah Goodman. Glycosylation. Difficulty of Studying Glycan Diversity. Unlike the Genetic Code, there is no glycan structure code. Glycans seen in prokaryotes may not be found in higher organisms.

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Evolution of Glycan Diversity and Cellular Organization of Glycosylation

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  1. Evolution of Glycan Diversity and Cellular Organization of Glycosylation Sarah Goodman

  2. Glycosylation

  3. Difficulty of Studying Glycan Diversity • Unlike the Genetic Code, there is no glycan structure code. • Glycans seen in prokaryotes may not be found in higher organisms. • Similar species may not show similar glycosylation. • Glycobiology is a relatively new field.

  4. Significant Glycans • N-linked glycans • O-linked glycans • Glycosphingolipids • Sialic Acids • Glycosaminoglycan chains

  5. N-Glycans In N-linked glycans, a sugar is linked to the N atom in the side chain of Asparagine or Arginine.

  6. N-Glycosylation Eukaryotes and Archaebacteria have the ability to manufacture N-glycans. Those produced in Archaea use a more diverse selection of sugars than those found in Eukaryotes.

  7. Examples of N-Glycans in Archaea N-Acetylglucosamine linked to Asparagine, found in Thermoplasma acidophilum. In Methanococcus maripaludis, the sugar is N-Acetylgalactose.

  8. N-Glycan Processing in Eukaryotes N-Glycosylation involves a dolichol oligosaccharide precursor. From this precursor, Glc3Man9GlcNAc2 is transferred to Asparagine residues. Next, the mannose sugars are trimmed. Plants and Animals Yeast and Slime Molds Do not form as complex N-glycans because they cannot trim the mannose sugars. Sometimes, they extend the chain of mannose sugars.

  9. O-Glycans In an O-linked glycan, a sugar is attached to the oxygen atom on the side chain of Serine, Threonine , orTyrosine.

  10. Evolutionary Distribution of O-Glycans Animals Plants Bacteria GalNAc O-linked to Serine or Threonine. Synthesized by GalNAc transferase. Arabinose O-linked to hydroxyproline. Galactose is O-linked to serine and threonine. Surface layers contain O-glycans, but little is known about their formation.

  11. Glycosphingolipids

  12. Evolutionary Trend Suggested by Glycosphingolipids

  13. Sialic Acids • Have only been found in deuterostomes. • Most complex sialic acids are found in invertebrates. • Simplest are found in humans. N- or O- substituted Neuraminic Acid

  14. Glycosaminoglycan Chains • Both have been found in invertebrates • Highly sulfated forms usually found in higher organisms. • Chondroitin sulfate chains are the most evolutionarily distributed glycosaminoglycan. • Are not found in plants, which have acidic pectin polysacharides instead. • Not found in bacteria. Heparan Sulfate Chondroitin Sulfate

  15. Glycophospholipid Anchors • Many Eukaryotes have glycophospholipid anchors containing the same core. • Usually are not found in Prokaryotes, but they can be found in the outer membranes of some protozoa.

  16. Molecular Mimickry Hyaluronan Group-A streptococcus Meningococci Polysialic Acid

  17. Location of Glycosylation

  18. Glycosylation Pathway Dolichol, part of the activated oligosaccharide precursor used by plants and animals in N-glycan processing. Glycosyltransferases catalyze the transfer of activated monosaccharide derivatives that serve as donors. These donors are synthesized in the cytoplasm.

  19. Membrane proteins created on the inside of vesicles appear on the outside of the cell.

  20. How well is glycosylation conserved among related species and within a species? • Very little data about this issue. • Sometimes it is conserved well, and sometimes not at all. • Most likely, glycan structure only needs to be conserved when the glycan has a very specific function. Immunoglobulin M, (1ADO) one of the antigens responsible for the different blood types.

  21. Selection Pressures for Glycosylation Both endogenous and exogenous selection pressures influence glycan evolution. Cells communicate with each other through glycans (endogenous) and pathogens recognize glycans to bind to their target cells (exogenous).

  22. The most glycan diversity is found on the ends of glycan chains, which is where recognition and binding would occur.

  23. Gene-Disruption Studies • One specific sialyltransferase enzyme in mice produces a specific terminus on vertebrate glycans found on B-cells and many other types of cells. • When the gene coding for this enzyme was disrupted, adverse affects were only seen in the B-cells, which had decreased signaling.

  24. The Red Queen Effect Pathogens Cells If every cell has the same type of receptor for a pathogen, a single pathogen could wipe out an entire colony.

  25. The Red Queen Effect However, if the glycan chains are diversified, a pathogen may only affect a few cells.

  26. Further Significance of Glycan Diversity • Glycan chains that don’t serve as receptors for pathogens can act as “decoys” by deterring the pathogens from finding the cells they are able to bind to. • For example, B-cells in mice contain a 6’-sialyllactosamine terminus, but so do many other cells. These other cells prevent pathogens from efficiently binding to the B-cells.

  27. Protective Glycan Variation • Erythrocytes carry the protein Glycophorin A, which contains may glycans. However, they are not suitable host cells for pathogens because they lack nuclei. • Pathogens binding to any of the glycans on Glycophorin A will not be able to reproduce. Glycophorin A (1AFO)

  28. Overall • Both endogenous and exogenous selection pressures played a role in the evolution of glycan processing pathways. • Additional gene-disruption studies and comparative glycobiology data would be helpful in furthering our understanding of glycosylation.

  29. References • Calo, Doron, Lina Kaminsky, and Jerry Eichler. "Protein glycosylation in Archaea: Sweet and extreme." Glycobiology 20.9 (2010): 1065–1076. Oxford Journals. Web. 17 June 2011. <http://glycob.oxfordjournals.org/content/20/9/1065.full.pdf+html>. • Gagneux, Pascal, and Ajit Varki. "Evolutionary considerations in relating oligosaccharide diversity to biological function." Glycobiology (Apr. 1999): 747-755. Oxford Journals. Web. 17 June 2011. <http://rcsb-class.rutgers.edu/Summer2011/files/evol-olig-diversity-1999.pdf>. • Varki, Ajit, Jeffrey D Esko, and Karen J Colley. Essentials of Glycobiology. 2nd ed. National Center for Biotechnology Information, n.d. Web. 17 June 2011. <http://www.ncbi.nlm.nih.gov/books/ NBK1926/>.

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