Biomedical Engineering Reference
In-Depth Information
Table 2.8 The potential roles and effects of the glycocomponent of glycoproteins. Reproduced from Walsh,
G. and Jefferies, R. (2006). Nature Biotechnology 24 , 1241-1252
Role/effect
Comment
Protein folding
Glycosylation can effect local protein secondary
structure and help direct folding of the polypeptide
chain
Protein targeting/traffi cking
The glycocomponent can participate in the sorting/
directing of a protein to its fi nal destination
Ligand recognition/binding
The carbohydrate content of antibodies, for example,
plays a role in antibody binding to monocyte
F c receptors and interaction with complement
component C1 q
Biological activity
The carbohydrate side chain of gonadotrophins is
essential to the activation of gonadotrophin signal
transduction
Stability
Sugar side chains can potentially stabilize a
glycoprotein in a number of ways, including
enhancing its solubility, shielding hydrophobic
patches on its surface, protection from proteolysis
and by direct participation in intrachain stabilizing
interactions
Regulates protein half-life
High levels of sialic acid (a family of acidic sugars
that often caps sugar side chains) can increase
a glycoprotein's plasma half-life. Exposure of
galactose residues can decrease plasma half-life by
promoting uptake via hepatic galactose residues.
Yeast glycosylation is of a 'high mannose' type,
which can also drive rapid removal from circulation
via specifi c cell-surface mannose receptors
Immunogenicity
Some glycosylation motifs characteristic of plant-
derived glycoproteins (often containing fucose
and xylose residues) are highly immunogenic in
mammals
additional glycosyltransferase-mediated trimming/modifi cation. The determinants of O-linked
glycosylation are even less well understood. Characteristic sequence recognition is not appar-
ent in most cases, and three-dimensional structural features may be more important in such
instances. Some glycosylated proteins will be characterized by one or more N-linked sugar side
chains, others by one or more O-linked side chains, and still others by both N- and O-linked
chains. Human EPO (Chapter 10), for example, displays three N-linked and one O-linked sugar
side chain.
For any glycoprotein, the exact composition and structure of the carbohydrate side chain can
vary slightly from one molecule of that glycoprotein to the next. This results in microheterogeneity
which can be directly visualized by analytical techniques such as isoelectric focusing (Chapter 7).
Also contributing to heterogeneity can be variable site glycosylation, in which some glycosylation
sites remain unoccupied within a proportion of the glycoprotein molecules. The overall basis of
heterogeneity is likely due to factors such as glycosyltransferase substrate specifi city and the fact
 
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