Lecture 6 OGalNac Glycans Ctype Lectins

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Lecture 6O-GalNac GlycansC-type Lectins
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The Glycome is Rich
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Examples of O-Glycans
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More O-glycans
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Even more.
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O-Glycosidic Linkage
O-glycosidic linkage is sensitive to alkali
(regardless of stereochemistry) b-elimination
GalNAc
H
O
H
H
H
a
H
O
C
C
H
Ser
O
OH
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Ribbon drawing of the ppGaNTase-T1 crystal
structure
Fritz, Timothy A. et al. (2004) Proc. Natl. Acad.
Sci. USA 101, 15307-15312
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Modeled binding of a MUC1 glycopeptide to
ppGaNTase-T1
Fritz, Timothy A. et al. (2004) Proc. Natl. Acad.
Sci. USA 101, 15307-15312
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Other Core O-Glycan Structures
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Cosmc

• Tn-antigens accumulate due to loss of b3Gal
  transferase activity
• No mutations in b3GalT message is expressed
• Missing Cosmc (Core 1 b3GalT -specific molecular
  chaperone, Xq23
• 25 identity, gt40 homology to b3GalT
• Absence of Cosmc results in proteosome
  degradation of b3GalT

Cosmc
Tn-antigen
T-antigen
Ju Cummings (2002) PNAS 9916613-8
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Is Cosmc a Chaperone?
T-synthase Mut Cosmc
T-synthase Wt Cosmc
His-tagged Cosmc HPC4 tagged T-synthase Ni
purification, Western with mAb to HPC4
T-synthase
Total
Bound to Ni
Not bound to Ni
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Outer Chain Assembly

• Sequential action of b4GalT and b3GlcNAcT gives
  rise to polylactosamine chains (Type II repeats)
• Type I repeats (Galb3GlcNAcb3) also occur

• GlcNAcb6Gal branches (I-antigen) can occur
• The ends of the chains are capped in a-linked
  sugars, e.g. a3/4Fuc and a3/6sialic acids
• Terminal structures make up important blood group
  determinants, e.g. the Lewis antigens

a
Ser/Thr
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Intestinal Epithelium stained with Periodic
acid-Schiffs Reagent
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Mucins
Dekker et al. (2002) TIBS 27126

• 11p15 family (MUC2, MUC5AC, MUC5B, MUC6) probably
  responsible for the formation of mucus layers
• 7q22 family (MUC3A, MUC3B, MUC12), 1q21 (MUC1),
  and 3q (MUC4, MUC13) are membrane mucins
• Mucin families are not necessairly related to
  each other, convergent evolution

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C-type Lectins
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Leukocyte Rolling
Tim Springer, Harvard
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