Protein Glycosylation: Implications for In Vivo Functions and Therapeutic Applications - Advances in Biochemical Engineering Biotechnology - page 157

in luminal regions are important for active Golgi retention [24].One mechanism
for retention is based on protein oligomerization in the environment of a speci-
fic Golgi cisterna, as in the case of

-2,6-ST. The oligomer is a disulfide bonded
dimer of the enzyme and is catalytically inactive as active site Cys residues
participate in dimerization. Under conditions of inadequate supply of donors
and/or substrate, the reactive sulfhydryls in the catalytic domain of one mole-
cule may interact with those of another. Only those that are continuously
supplied with donor and substrate resist disulfide bond formation and remain
active. The disulfide bonded dimer acts primarily as a Gal-specific lectin in the
Golgi to retain unsialylated molecules and pass them off to the active ST for
sialylation [25].
Proteins that do not reside in ER exit at specialized regions adjacent to the
Golgi. Within the Golgi, different subcompartments are distinguishable (cis-,
medial- and trans-Golgi) on the basis of a distinct content of glycan processing
enzymes. Adjacent to the trans-Golgi cisternae is a network of tubules located
with coated buds and vesicles that is called the trans-Golgi network (TGN)
where sorting of proteins destined to specific intracellular compartments or cell
surface domains from constitutively secreted proteins occurs [26].The secretory
pathway involves vesicular transfer to the plasma membrane followed by the
secretory event, that is exocytotic discharge of vesicle contents [27].

a

2.3
Asparagine-Linked Glycosylation

A number of different types of protein glycosylations described in the literature
[28, 29] are shown in Table 1. N -Glycans are characterized by a

b -glycosidic

linkage between a Gn residue and the amide N of an Asn residue.Though there

are many different Asn-glycans, the common feature is the presence of a penta-
saccharide (Man 3 Gn 2 ) core because they all arise from the same biosynthetic
precursor lipid-like oligosaccharide that is transferred to the nascent peptide
chains. The core can have a Fuc attached to the Gn that is linked to the Asn, and
can possess a bisecting Gn residue attached to the central Man of the core. The
N -linked glycans fall into three main subgroups as shown in Fig. 1. These are as
follows.

d

1. High-Man structures contain 2-6 additional Man residues at the two ter-
minating Man residues of the core and vary in the number, position and
degree of phosphorylation or sulfation of Man residues.
2. Complex-type structures have 2-4 lactosamine (Gal

1,4-Gn) units distribu-
ted over the two outer Man residues of the core forming bi-, tri-, or tetra-
antennary structures. Each of the arms can terminate in sialic acid forming
sialyllactosamine. Sulfated lactosamine has been found to substitute sialyl-
lactosamine in some cases, such as the glycoprotein hormones LH, FSH and
TSH. Other complex-type structures contain polylactosamine in their outer
chains, as in erythroglycan.

b