Biomedical Engineering Reference
In-Depth Information
Fig. 5. The mucine type O -linked glycans:
-GalNAc;
-Gal;
-SA
site composed of nine subsites with the acceptor Ser/Thr in the centre. The
model postulates independent interactions of the nine amino acid moieties with
their respective binding sites [55]. However, no consensus sequence has emerg-
ed due to the broad range of residues that the binding site of GalNAcT can
accommodate, and due to the existence of multiple isoforms of GalNAcT with
overlapping specificities [56]. The distribution of charged amino acids flanking
the O -glycosylation site can have a large influence on glycosylation, with posi-
tion -1 relative to the glycosylation site being particularly sensitive.A combina-
tion of acidic residues at positions -1 and +3 almost completely eliminates
glycosylation.An amino acid change resulting in de novo attachment of O -link-
ed glycan on glycoprotein hormone common
-subunit has been reported [57].
There are seven different types of O -glycans available in nature [29], amino
acids to which glycosylation occur and corresponding O -linked sugars have been
shown in Table 1. Analysis of mucin type glycosylation revealed that Pro occurs
at increased frequency at positions -1 and +3 relative to the glycosylation site
[58]. The acceptor sequence context for O -glycosylation of Ser was found to
differ from that of Thr, and showed a high abundance of Pro, Ser and Thr. In
general, the O -glycosylation sites are found to cluster and to have a high abun-
dance in the N -terminus of the protein. The sites are also found to have an in-
creased preference for different classes of
a
-turns. Pro in positions -1 and +1 is
speculated to function as 'gating' residue favouring O - and inhibiting N -glycosy-
lation [29].
b
2.5
Glucosylphosphatidylinositol (GPI) Anchors
Anchoring of surface membrane proteins (e.g. receptors) via GPI anchors is a
major means in eukaryotic cells. All GPI anchors analysed contain a common
glycan core (Man
1-4GlcNH). This may be further proces-
sed in cell and protein specific manner. Nascent proteins destined to be GPI-
anchored contain, besides the amino terminal signal peptide that is typical of
proteins processed in ER, a second hydrophobic peptide at their C -terminus
which is also removed during processing. The GPI moiety is linked to what had
been an internal sequence in the nascent protein. The subject matter of assemb-
ly of GPI anchors [59] and GPI anchored membrane proteins [60] have been
reviewed recently.
a
1-2Man
a
1-6Man
a
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