Biomedical Engineering Reference
In-Depth Information
UDP-Glc: gycoprotein
glucosyltransferase
Fig. 4. A model for the involvement of calnexin in quality control mechanism in ER.Associa-
tion and disengagement of calnexin depend on the folding status of the semiprocessed glyco-
protein. Calnexin recognizes partially trimmed monoglucosylated glycans, generated either
by glucose trimming or by reglucosylation pathways. Symbols and abbreviations are same as
Fig. 3 (adopted from [45])
folding and disulfide bond formation may determine extent of core N -glycosy-
lation [39].Analysis of glycosylation site-occupancy has revealed that glycosyla-
tion of potential target sequons is more likely to occur near the N- than the C -ter-
minus of a protein [36].
The glycan that is transferred to the protein is a substrate for a variety of pro-
cessing
-Gs and GlycTs to give mature high Man or complex-type chains as
given in Fig. 3 [40].The glycan is processed in terms of removal of three Glc resi-
dues by stepwise action of
a
-G II. The Glc trimming affects glycopro-
tein exit from the ER. A quality control procedure ensures that proteins which
are incompletely folded, or incorrectly oligomerized, are not transported out of
the ER so long as they have not acquired “export competent conformation”[41].
Quality control and degradation depend on glycosylation as deglycosylated
species are stably retained in ER, as observed for Na, K-ATPase
a
-G I and
a
-subunit [42].
The role of Glc residues in protein folding and quality control has been clarified
by the identification of two lectin-like proteins in the ER - calnexin and calre-
ticulin; the latter is lumenal while the former is a transmembrane molecular
chaperone protein [43, 44]. Calnexin is believed to recognize partially trimmed
monoglucosylated (Glc 1 Man 9 Gn 2 ) glycans on newly synthesized glycoproteins
and detain them in the ER until properly folded. Monoglucosylated chains may
be generated via two mechanisms - cotranslational processing of immature
Glc 3 Man 9 Gn 2 glycans (the Glc trimming pathway) by
b
-G II, or re-
glucosylation of fully trimmed Man 8-9 Gn 2 glycans by lumenal UDP-Glc:glyco-
a
-G I and
a
Search WWH ::




Custom Search