Biomedical Engineering Reference
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protein glucosyltransferase (reglucosylation or salvage pathway). A model pro-
posed for the involvement of calnexin in quality control of influenza hemagglu-
tinin (HA) is shown in Fig. 4. The glucosyltransferase preferentially acts on
unfolded proteins and functions as a major sensor for incompletely folded pro-
teins in ER. During folding, a glucopeptide cycle is formed between fully trim-
med and monoglucosylated glycans. Depending upon folding status, the glyco-
protein enters into the de- and reglucosylation cycle. Properly folded protein
escapes the reglucosylation step, and the deglucosylated form is liberated from
the calnexin anchor for subsequent processing. Proteins that fail to attain the
correct conformation or have assembled into non-native aggregates are retained
in ER, and degraded by ubiquitin-proteasome system [46]. It may be noted that
the calnexin-calreticulin mediated folding pathway is not the only pathway to be
followed in the glycosylation of proteins; other chaperones seem to be involved
for protein folding.
Furthermore,
-M efficiently removes a single terminal Man residue to gener-
ate Man
8
Gn
2
in the ER.The action of ER
a
-M perhaps alters the conformation of
the glycoprotein, making it more susceptible to the Golgi
a
a
-M I. The concerted
efforts of ER and Golgi
-Ms may be required for fine tuning mechanism to pro-
duce surface glycoproteins with particular assortments of high Man type chains
[47]. In Golgi, Man chains are processed in two steps by the action of
a
a
-M II, active in the medial-Golgi, resulting in
the removal of additional five Man to yield Man
3
Gn
2
[48].The processing of Man
chains is obligatory for the formation of complex-type glycans. In medial Golgi,
GnT I inserts Gn residue to
-M I, active in the cis-Golgi and
a
a
1,3-linked Man followed by the cleavage of two
terminal Man by the action of
1,6-linked
Man by GnT-II takes place in the medial Golgi. In case of mammalian cells, only
occasionally, but in plant cells generally, Fuc residue is also incorporated at this
stage in the medial-Golgi by the action of
a
-M II.Addition of another Gn to the
a
-FT.The termination of glycan chain
occurs in the trans-Golgi by the incorporation of Gal and SA with the help of
GalT and ST, respectively. Thus, a complex-biantennary
N
-glycan is synthesized
before secretion (Fig. 3).In different cell types,diversity in structural features of
N
-linked oligosaccharides is obtained, although these are not included in Fig. 3.
As an example, GnT III catalyzes the addition of Gn in
a
-linked
Man of the core producing a bisecting Gn residue, and controls the branching
patterns in vivo [49]. Amongst other terminal glycosylation, incorporation of
GalNAc,sulfation,and
O
-acetylation of SAs are important, also occurring in the
trans-Golgi, which is again cell specific. The turnover of terminal glycans is
much faster than that of the protein molecule, and the core sugars exhibit a
turnover rate similar to that of the protein [50].
b
1,4-linkage to
b
2.3.2
Factors Regulating Asn-Linked Glycosylation
Despite the fact that the
N
-linked glycans are derived from the same precursor,
with few exceptions each glycosylated site in a glycoprotein is associated with
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