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.
• Similar species may not show similar
glycosylation.
• Glycobiology is a relatively new field.
Significant Glycans
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•
•
•
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N-linked glycans
O-linked glycans
Glycosphingolipids
Sialic Acids
Glycosaminoglycan chains
N-Glycans
In N-linked
glycans, a
sugar is
linked to the
N atom in the
side chain of
Asparagine or
Arginine.
N-Glycosylation
Eukaryotes and
Archaebacteria
have the ability to
manufacture Nglycans. Those
produced in
Archaea use a
more diverse
selection of sugars
than those found
in Eukaryotes.
Examples of N-Glycans in Archaea
N-Acetylglucosamine linked to Asparagine, found
in Thermoplasma acidophilum. In Methanococcus
maripaludis, the sugar is N-Acetylgalactose.
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.
Do not form as complex Nglycans because they
cannot trim the mannose
sugars. Sometimes, they
extend the chain of
mannose sugars.
O-Glycans
In an O-linked
glycan, a sugar is
attached to the
oxygen atom on
the side chain of
Serine, Threonine ,
orTyrosine.
Evolutionary Distribution of O-Glycans
Animals
GalNAc Olinked to
Serine or
Threonine.
Synthesized by
GalNAc
transferase.
Plants
Arabinose Olinked to
hydroxyproline.
Galactose is Olinked to serine
and threonine.
Bacteria
Surface layers
contain Oglycans, but little
is known about
their formation.
Glycosphingolipids
Evolutionary Trend Suggested by
Glycosphingolipids
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
Glycosaminoglycan Chains
Heparan Sulfate
Chondroitin Sulfate
• 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.
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.
Molecular Mimickry
Group-A streptococcus
Meningococci
Hyaluronan
Polysialic Acid
Location of Glycosylation
Most cell-surface protein synthesis takes place in the rough ER.
Proteins are transferred to the Golgi apparatus through an
intermediate compartment.
In the Golgi, proteins are modified by glycosyltransferases.
Glycosylation Pathway
• Glycosyltransferases catalyze the transfer of
activated monosaccharide derivatives that serve
as donors.
• These donors are synthesized in the cytoplasm.
Dolichol, part of the activated oligosaccharide precursor
used by plants and animals in N-glycan processing.
Membrane proteins
created on the inside
of vesicles appear on
the outside of the
cell.
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.
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).
The most glycan diversity is found on the ends of glycan
chains, which is where recognition and binding would occur.
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.
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.
The Red Queen Effect
However, if the glycan chains are diversified, a
pathogen may only affect a few cells.
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 Bcells.
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)
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.
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://rcsbclass.rutgers.edu/Summer2011/files/evol-olig-diversity1999.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/>.