Biomedical Engineering Reference
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still in an unfolded state [30]. Initial steps in this pathway, which appear to be
generally conserved, involve the synthesis in ER membrane of a dolichol linked
precursor glycan and its transfer to an Asn residue of the growing peptide chain.
The major steps in phosphodolichol pathway of protein
N
-glycosylation have
been reviewed [31]. The principal pathway for biosynthesis of the dolichol-
linked oligosaccharides is shown in Fig. 2.The oligosaccharyl transferase (OST)
is integral to ER membrane, with active site of the enzyme residing near the
membrane on the lumenal side, and transfer only occurs when 12-14 amino
acids
C
-terminal to a sequon have been translocated into the ER lumen [33].The
glycan is added to Asn residue in the tripeptide consensus sequence Asn-
X-Ser/Thr (X=any amino acid) and presence of Thr rather than Ser at the
hydroxy position favors efficient glycosylation [34]. The OH group of the
Thr/Ser has a role in explaining the unique reactivity of this Asn with the DolPP
sugar derivative. Secondary structure prediction analysis suggested that these
tripeptide consensus sequences have a high probability of occurring in a
-turn
or other loop structures, which could serve as recognition sites for enzymes
involved in glycosylation [35]. Analysis of occurrence of amino acids at posi-
tions around the glycosylated Asn (given the position zero) indicates that Pro is
rarely allowed at position +3 and is never observed at position +1 [36].Asp,Glu,
Leu and Trp at position +1 are also associated with inefficient glycosylation [37].
This position is preferentially occupied by non-bulky amino acids such as Gly,
Val and Ala.
b
Fig. 2.
Pathway of biosynthesis of the dolichol-linked oligosaccharide.
-UDP: GlcNAc-Uridine
diphosphate;
-PPDol: GlcNAc-Pyrophosphatedolichol;
-GDP: Man-Guanosine diphosphate;
-Pdol: Man-Phosphodolichol;
-Pdol: Glc-Phosphodolichol. (adopted from [32])
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