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Transcript of Glycobiology Introduction to GlycobiologyIntroduction to Glycobiology Glycan structuresGlycan...
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
Light microscopy micrograph of Cryptococcus neoformans capsule delineated by India ink. The inner circle represents the fungal cell, with the wide outer circle being the capsule.Steenbergen et al. (2003) Microbes and Infection 5:667
Scanning electron microscopy of C. neoformans yeast cells.Van Duin et al. (2004) Antimicrobial Agents and Chemotherapy 48:2014
Light microscopy micrograph of Cryptococcus neoformans
Steenbergen et al. (2003) Microbes and Infection 5:667
What if a MAJOR cell component was invisible by standard microscopy?
The Eukaryotic Cell SurfaceThe Eukaryotic Cell Surface
Tiny sugar “decorations”..added as an afterthought
Lodish, et al. (1995) Molecular Cell Biology 3rd ed.Lodish, et al. (1995) Molecular Cell Biology 3rd ed.
??
The “glycocalyx” surrounding a fibroblast – glycans stained blackThe “glycocalyx” surrounding a fibroblast – glycans stained black
lipid bilayerlipid bilayer
fibroblastfibroblast
extracellularextracellular
intracellularintracellular
Martinez-Palomo, A., et al. Cancer Res. 29, 925-937, 1969
The Cell Surface -- The Real PictureThe Cell Surface -- The Real Picture
““Evolution has failed to generate a living cell Evolution has failed to generate a living cell devoid of surface glycosylation” devoid of surface glycosylation” - A. Varki- A. Varki
““Every eukaryotic cell is covered with a dense and complex array Every eukaryotic cell is covered with a dense and complex array of glycans, which also feature prominently in extracellular matrix of glycans, which also feature prominently in extracellular matrix and secreted soluble molecules.” … in fact…and secreted soluble molecules.” … in fact…
Tropical Forest
Canopy
Ajit Varki, “Perspectives on the Future of Glycobiology,” Athens, GA, 14-Mar-2011
Tropical Forest
Canopy
Cohen & Varki (2010) OMICS 4:455
lipid bilayerlipid bilayer
fibroblastfibroblast intracellularintracellular
Martinez-Palomo, A., et al. Cancer Res. 29, 925-937, 1969
The Cell SurfaceThe Cell Surface
Real image textbook imageReal image textbook image
Sharon and Lis (1993) Scientific American
Cell-cell recognition is one important functionCell-cell recognition is one important function
Lectin
Glycan
Life cycle of the influenza virus - the role of glycansLife cycle of the influenza virus - the role of glycans
Influenza jumps from animals to humans via a Influenza jumps from animals to humans via a slight change in glycan binding specificityslight change in glycan binding specificity
Stevens, et al. (2006) Nat Rev Microbiol. 4:857-64
Influenza jumps from animals to humans via a Influenza jumps from animals to humans via a slight change in glycan binding specificityslight change in glycan binding specificity
Stevens, et al. (2006) Nat Rev Microbiol. 4:857-64
Inflammation: How we fight bacterial infection
Leukocyte cell surface glycan ligand Leukocyte cell surface glycan ligand required for endothelial recognitionrequired for endothelial recognition
R
Marquardt, et al. (1999) J. Pediatr. 134, 681
You fight bacterial infection using glycans. This You fight bacterial infection using glycans. This child could not …child could not …
Marquardt, et al. (1999) Blood 94, 3976
……until he was fed FUCOSE (a sugar), after which…until he was fed FUCOSE (a sugar), after which…
“…“…neutrophil levels returned to the normal range .... neutrophil levels returned to the normal range .... there were no further infections”there were no further infections”
CD59, a complement CD59, a complement defense glycoproteindefense glycoprotein
20 kDa protein3 kDa N-linked
glycan
1 kDa O-linked
glycan
1.5 kDa GPI
anchor
Proteins typically fold onto themselves, Proteins typically fold onto themselves, whereas glycans spread out in spacewhereas glycans spread out in space
plasma membrane
plasma membrane
Glycoprotein Glycolipid
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
Monosaccharides equilibrate between open chain and ring forms.Monosaccharides equilibrate between open chain and ring forms.For each monosaccharide, two ring forms (anomeric For each monosaccharide, two ring forms (anomeric
configurations) are possible, configurations) are possible, αα and and ββ
Seven sugars and their structural relationship to glucoseSeven sugars and their structural relationship to glucose
Two important terminal sugarsTwo important terminal sugars
When a glycosidic bond is formed,When a glycosidic bond is formed,the anomeric configuration is “locked”the anomeric configuration is “locked”
Nomenclature:Nomenclature:
-Name the non-reducing (left-most) sugar (Gal)-Name the non-reducing (left-most) sugar (Gal) -Name the anomeric configuration ( -Name the anomeric configuration (ββ)) -Name the anomeric carbon number (1) -Name the anomeric carbon number (1) -Name the substituted carbon number (4) -Name the substituted carbon number (4) -Name the substituted sugar (Glc) -Name the substituted sugar (Glc)
RESULT: Gal RESULT: Gal ββ1-4 Glc1-4 Glc
NeuAc α2-3 Gal β1-4 (Fuc α1-3) GlcNAcNeuAc α2-3 Gal β1-4 (Fuc α1-3) GlcNAc
Nomenclature: Branches are placed in parenthesesNomenclature: Branches are placed in parentheses
NeuAc α2-3 Gal β1-4 (Fuc α1-3) GlcNAcNeuAc α2-3 Gal β1-4 (Fuc α1-3) GlcNAc
Molecular diversity glycansMolecular diversity glycans
PolypeptidesPolypeptides GlycansGlycans
Building blocksBuilding blocks amino acidsamino acids monosaccharidesmonosaccharides
Number of different monomersNumber of different monomers 20 common20 common 9 common9 common
Linkage sites per monomerLinkage sites per monomer 11 3-43-4
Possible linkage configurationsPossible linkage configurations 11 22
Possible homodimer structuresPossible homodimer structures 11 6-86-8
Linkage modesLinkage modes linearlinear linear or branchedlinear or branched
HO
HO
O
HO
O
GalHO
OHO
HO
O
HO
O
GalHO
O
H2N C
Ala
OH
OH2N C
Ala
OH
O
Three different amino acids (Ala, Ser, Tyr) – 6 structuresThree different amino acids (Ala, Ser, Tyr) – 6 structures
Ala-Ser-TyrAla-Ser-TyrAla-Tyr-SerAla-Tyr-SerSer-Ala-TyrSer-Ala-TyrSer-Tyr-AlaSer-Tyr-AlaTyr-Ala-SerTyr-Ala-SerTyr-Ser-AlaTyr-Ser-Ala
Three different sugars (Glc, Gal, Man) – 1,056 structures …Three different sugars (Glc, Gal, Man) – 1,056 structures …
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
““N-linked” glycan linkage to protein asparagine residuesN-linked” glycan linkage to protein asparagine residues
Families of N-linked glycan structuresFamilies of N-linked glycan structures
Man
4GlcNAc1
2Man
Man
Man
Man
2Man
2Man
2Man
63
Man63 4GlcNAc1 Asn
4GlcNAc1
Man62
Man63 4GlcNAc1 Asn
Man42
4GlcNAc1
4GlcNAc1
4GlcNAc1
4GlcNAc1
6Gal
6Gal
6Gal
6Gal
NeuAc
NeuAc
NeuAcNeuAc
4GlcNAc1
Man
Man63 4GlcNAc1 Asn
2Man4GlcNAc13GalNeuAc
Man
Man
63
core
core
core
High Mannose
Complex
Hybrid
Diversity in complex N-linked glycan structureDiversity in complex N-linked glycan structure
4GlcNAc1
Man642
Man643
4GlcNAc1 Asn
Man42
4GlcNAc1
4GlcNAc1
6Gal
6Gal
NeuAc
4GlcNAc16GalNeuAc
4GlcNAc16GalNeuAc
NeuAc4GlcNAc16GalNeuAc
GlcNAc1
Fuc
6
Examples of structures found as termini on the branches of complex Examples of structures found as termini on the branches of complex N-linked glycoprotein glycans….N-linked glycoprotein glycans….
Terminal Saccharide Diversity --- A key to recognitionTerminal Saccharide Diversity --- A key to recognition
NeuAc NeuAc 2-6 Gal 2-6 Gal 1-4 GlcNAc---1-4 GlcNAc---NeuAc NeuAc 2-3 Gal 2-3 Gal 1-4 GlcNAc---1-4 GlcNAc---
Gal Gal 1-3 Gal 1-3 Gal 1-4 GlcNAc---1-4 GlcNAc---4-SO4-SO33-GalNAc -GalNAc 1-4 GlcNAc---1-4 GlcNAc---
(-Gal (-Gal 1-4 GlcNAc 1-4 GlcNAc 1-3-)1-3-)nn = polylactosamine repeats (n may be >6) = polylactosamine repeats (n may be >6)
(-NeuAc (-NeuAc 2-8-) 2-8-) nn = polysialic acid (n may be >50) = polysialic acid (n may be >50)
Fuc residues (e.g. Fuc Fuc residues (e.g. Fuc 1-21-2 Gal; Fuc Gal; Fuc 1-3 GlcNAc; Fuc 1-3 GlcNAc; Fuc 1-4 GlcNAc1-4 GlcNAc
Glycoforms add yet more variation-- Glycoforms add yet more variation--
Whereas a protein is defined by its unique amino acid Whereas a protein is defined by its unique amino acid sequence, sequence, the glycan structure at a single protein the glycan structure at a single protein glycosylation site variesglycosylation site varies. .
Although glycan structures vary at each glycosylation Although glycan structures vary at each glycosylation site, the profile is reproducible, protein-specific, site-site, the profile is reproducible, protein-specific, site-specific, and cell type-specific.specific, and cell type-specific.
Three glycoforms of CD59Three glycoforms of CD59
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
“O-linked” glycan linkage to protein serine residues
Examples of variations of O-linked glycans
GalNAc Serine
GalNAc Serine
NeuAc 26
GalNAc Serine
Gal 1
NeuAc 263
GalNAc SerineNeuAc 2-3 Gal 1
NeuAc 263
Gal 1-4 GlcNAc 1
Fuc 1
GalNAc Serine
GlcNAc 1
63
4NeuAc 2-3 Gal 1
3
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
GPI (glycosylphosphatidylinositol) anchored proteinGPI (glycosylphosphatidylinositol) anchored protein
Gal 2Gal62Gal
Gal
Man 2Man
Man63 4GlcNH2
1 6myo Inositol1
P=O
O
O
O
O
CH2
CH2
NHC
O
Asp
[Phosphoethanolamine]
6
P=O
O
O
O
O
CH2CH CH2
[Phosphatidylinositol]
20 kDa protein3 kDa N-linked
glycan
1 kDa O-linked
glycan
1.5 kDa GPI
anchorplasma membrane
CD59, a complement defense glycoproteinCD59, a complement defense glycoprotein
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
GlycoproteinsGlycoproteins• N-LinkedN-Linked
• O-LinkedO-Linked
• GPI AnchorGPI Anchor
• O-GlcNAcO-GlcNAc
*A non-inclusive list!*A non-inclusive list!
O-GlcNAc
Note: No further sugar substitutions have been confirmed
O-GlcNAc is localized to the cytoplasm and nucleus.O-GlcNAc is localized to the cytoplasm and nucleus.
O-GlcNAc is present in all higher eukaryotes studied.O-GlcNAc is present in all higher eukaryotes studied.
O-GlcNAc is as abundant as phosphorylation.O-GlcNAc is as abundant as phosphorylation.
UDP-GlcNAc is as abundant as ATP in some cell types. UDP-GlcNAc is as abundant as ATP in some cell types.
O-GlcNAc containing proteins are phosphoproteins.O-GlcNAc containing proteins are phosphoproteins.
O-GlcNAc and phosphorylation are often reciprocal.O-GlcNAc and phosphorylation are often reciprocal.
O-GlcNAc is dynamic, implying a regulatory role.O-GlcNAc is dynamic, implying a regulatory role.
Key Features of O-linked GlcNAc
Three-state model: unmodified / O-GlcNAc / phosphate
O-GlcNAc
GlycoproteinGlycoproteinUnmodified protein
Unmodified proteinPhosphoprotein
OPO32-
PhosphatasePhosphatase
OGTOGT
OGTOGT
PhosphatasePhosphatase
KinaseKinase
KinaseKinase
O-GlcNAcaseO-GlcNAcase
O-GlcNAcaseO-GlcNAcase
Natasha Zachara
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
A GlycosphingolipidA Glycosphingolipid
Galactosylceramide (GalCer)Galactosylceramide (GalCer)
HO
HO
O
HO
O
NH
HO
Gal Sphingosine
Ceramide
HO
A GangliosideA Ganglioside
““GD1a”GD1a”
HO
OO
HO
HOOHO
O
HO
HOHO
O
HO
NH
HOHO
O
H3COH3C
NH
H3CNH
OO
HO
O
NH
HO
GlcGalGalGalNAcNeuAc
NeuAc
Sphingosine
Ceramide
Glycolipids are the major glycoconjugates in the brainGlycolipids are the major glycoconjugates in the brain
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
Major Glycoconjugates of EukaryotesMajor Glycoconjugates of Eukaryotes
• GlycoproteinsGlycoproteins
• GlycolipidsGlycolipids
• ProteoglycansProteoglycans
Glycosaminoglycans (GAG’s) Glycosaminoglycans (GAG’s) and Proteoglycansand Proteoglycans
• GLYCOSAMINOGLYCANS (GAG’s)GLYCOSAMINOGLYCANS (GAG’s)– long linear glycans made of repeating long linear glycans made of repeating
disaccharidesdisaccharides– Hyaluronic acid is the only “stand-alone” Hyaluronic acid is the only “stand-alone”
GAG, other GAG’s are constituents of …GAG, other GAG’s are constituents of …
• PROTEOGLYCANSPROTEOGLYCANS– GAG’s on proteinsGAG’s on proteins– Defined by their repeating disaccharide unitsDefined by their repeating disaccharide units– GAG’s on proteoglycans are sulfatedGAG’s on proteoglycans are sulfated
Hyaluronic acid -- a “simple” Hyaluronic acid -- a “simple” space filling moleculespace filling molecule
(GlcU β4 GlcNAc)(GlcU β4 GlcNAc)nn
Post-polymerization variations in glycosaminoglycansPost-polymerization variations in glycosaminoglycans
Proteoglycans
disaccharide (A-B)n
NameMol. Wt.(daltons) A B
Sulfates perdisaccharide
Linked toprotein? Core Tissue distribution
hyaluronicacid
up to 8 x 106 GlcA GlcNAc 0 N NAconnective tissue,skin, vitreoushumor, cartilage,synovial fluid
chondroitinsulfate
5,000 -50,000 GlcA GalNAc 0.2 - 2.3 Y Gal-Gal-Xyl
cartilage, cornea,bone, skin, arteries
dermatansulfate
15,000 -40,000
GlcA orIdA
GalNAc 1.0 - 2.0 Y Gal-Gal-Xylskin, bloodvessels, heart,heart valves
heparansulfate
5,000 -12,000
GlcA orIdA
GlcNAc 0.2 - 2.0 Y Gal-Gal-Xyllung, arteries, cellsurfaces, basallaminae
heparin6,000 -25,000
GlcA orIdA GlcNAc 2.0 - 3.0 Y Gal-Gal-Xyl
lung, liver, skin,mast cells
keratansulfate
4,000 -19,000 Gal GlcNAc 0.9 - 1.8 Y
N- and O-linkedglycoproteins
cartilage, cornea,intervetebral discs
Cartilage proteoglycanCartilage proteoglycan
Cartilage proteoglycanCartilage proteoglycan
fibroblast
extracellular
intracellular
Squamus Epithelium
Glycoproteins and glycolipids are found prominently on extracellular leaflet of the plasma membrane and on the intralumenal leaflet of lysosomes. They also are found in the ER and Golgi apparatus, where they are synthesized. GAG’s and proteoglycans are found on the cell surface and as prominent structures of the extracelllular matrix.
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functionsGlycan functions
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition
• General principlesGeneral principles• Influenza virusInfluenza virus• InflammationInflammation
– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition
• General principlesGeneral principles• Influenza virusInfluenza virus• InflammationInflammation
– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
Sharon and Lis (1993) Scientific American
Carbohydrate binding determinant
Carbohydrate recognition domain (CRD)
Glycans in cell-cell recognitionGlycans in cell-cell recognition
Lectin
Glycan
Sialoadhesin CRDSialoadhesin CRD
May, A.P., et al. (1998) Mol. Cell 1, 719-728
Principles of glycan-Principles of glycan-lectin binding:lectin binding:
-hydrogen bonds -hydrogen bonds -hydrophobic stacking-hydrophobic stacking-multivalent binding-multivalent binding-(salt bridges)-(salt bridges)-(calcium coordination)-(calcium coordination)
May, A.P., et al. (1998) Mol. Cell 1, 719-728
Sialic acid
glycerol
carboxylate
acetyl
Comb & Roseman, J Am Chem Soc 80, 497 (1958)
Sialic acids --Sialic acids -- Enhanced roles in glycan recognition Enhanced roles in glycan recognition
Diverse sialic acid glycans at the cell surfaceDiverse sialic acid glycans at the cell surface
Essentials of GlycobiologySecond Edition
sialic acid
Diverse sialic acid linkages at the cell surfaceDiverse sialic acid linkages at the cell surface
NeuAc-α2,3-Gal-β1,4-GlcNAc NeuAc-α2,6-Gal-β1,4-GlcNAc
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition
• General principlesGeneral principles• Influenza virusInfluenza virus• InflammationInflammation
– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
Life cycle of the influenza virus - the role of sialic acidsLife cycle of the influenza virus - the role of sialic acids
Influenza virus hemagglutinin (side and top views, arrows are sugar binding sites)
Sialoglycan structure drives biological recognition:Sialoglycan structure drives biological recognition:Influenza pandemics are determined by sialic acid linkage specificityInfluenza pandemics are determined by sialic acid linkage specificity
Stevens et al (2006) Nat Rev Microbiol. 4:857-64
Influenza virus Influenza virus neuraminidaseneuraminidase
(sialidase)(sialidase)
Rational design of an anti-influenza drug based on Rational design of an anti-influenza drug based on sialic acid binding to the viral neuraminidasesialic acid binding to the viral neuraminidase
1
2
345
67
89
OH
HO
HO
OOR
NH
OH
COOH
NH
NH
NH2
OH
HO
ONH
OH
COOH
O
O
NH2
NH
O
COOR
O
Sialic Acid Relenza Tamiflu
Influenza virus Influenza virus budding in vitro budding in vitro
without (top) and without (top) and with (bottom) with (bottom)
neuraminidase neuraminidase inhibitorinhibitor
Prophylactic efficacy of a sialic acid-based Prophylactic efficacy of a sialic acid-based influenza neuraminidase inhibitorinfluenza neuraminidase inhibitor
Peters, P.H., et al. (2001) J Am Geriatr Soc 49, 1025
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition
• General principlesGeneral principles• Influenza virusInfluenza virus• InflammationInflammation
– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
Inflammation: How we fight bacterial infection
Leukocyte adhesion to E-selectin transfected COS cells
Selectin
glycoconjugate
Endothelium
Neutrophil
Leukocyte cell surface glycan ligand Leukocyte cell surface glycan ligand required for endothelial recognitionrequired for endothelial recognition
R
Marquardt, et al. (1999) J. Pediatr. 134, 681
Leukocyte adhesion deficiency (LAD) Type IILeukocyte adhesion deficiency (LAD) Type II
Human blood group antigens and Selectin ligandsHuman blood group antigens and Selectin ligands
Fuc 1-2 Gal 1- O (H) Blood Type
Fuc 1-2 Gal 1- A Blood Type |
GalNAc 1-3
Fuc 1-2 Gal 1- B Blood Type |
Gal 1-3
Gal 1- Bombay Phenotype
NeuAc 2-3 Gal 1-4 GlcNAc- Selectin ligand |
Fuc 1-3
NeuAc 2-3 Gal 1-4 GlcNAc- LAD Type II
““Within days of starting fucose therapy, neutrophil levels returned to the Within days of starting fucose therapy, neutrophil levels returned to the normal range .... there were no further infections and antibiotic normal range .... there were no further infections and antibiotic prophylaxis was discontinued.”prophylaxis was discontinued.”
Marquardt, et al. (1999) Blood 94, 3976
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
Hyaluronic acid -- a “simple” Hyaluronic acid -- a “simple” space filling moleculespace filling molecule
(GlcU β4 GlcNAc)(GlcU β4 GlcNAc)nn
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
GlycobiologyGlycobiology
• Introduction to GlycobiologyIntroduction to Glycobiology
• Glycan structuresGlycan structures
• Glycan functions Glycan functions – RecognitionRecognition– Biophysical effectsBiophysical effects– Biochemical effectsBiochemical effects
Anticoagulant carbohydrate determinantAnticoagulant carbohydrate determinant
Reference textsReference textsReference textsReference texts
Oxford University Press, New YorkOxford University Press, New York Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Content freely available at: Content freely available at: http://www.ncbi.nlm.nih.gov/books/NBK1908http://www.ncbi.nlm.nih.gov/books/NBK1908
Introduction to GlycobiologyIntroduction to GlycobiologyME:330.712ME:330.712
Mar-April 2013Mar-April 2013
Introduction to GlycobiologyIntroduction to GlycobiologyME:330.712ME:330.712
Mar-April 2013Mar-April 2013
Course co-directors: Course co-directors: Ronald Schnaar ([email protected])Ronald Schnaar ([email protected]) Natasha Zachara ([email protected])Natasha Zachara ([email protected])
© 2012 The National Academy of Sciences