Virion polypeptides
HSV-1 virions has been suggested to contain at least
30 distinct proteins.
They were designated VP and given serial numbers.
All of the virion proteins were made after infection, and no host proteins could be detected in virion preparations.
At least
11 are on the surface of the virion (accessable to antibody) and at least
10 are glycosylated.
GLYCOSYLATION -
the enzymatic process that links saccharides to produce glycans, attached to proteins,
lipids,
or other organic molecules.This enzymatic process produces one of the fundamental biopolymers found in cells (along with DNA, RNA, and proteins).
Glycosylation is a form of
co-translational and post-translational
modification. 1]
The majority of proteins synthesized in the rough ER undergo glycosylation.
It is an enzyme-directed
site-specific process, as opposed to the non-enzymatic chemical
reaction of glycation.
Glycosylation is also present in the
cytoplasm and nucleus as the O-GlcNAc modification.
Five classes of
glycans are produced:
The
carbohydrate chains attached to the target proteins serve various
functions.
[2]
For instance, some proteins
do not fold correctly unless they are
glycosylated first.
[1]
Also, polysaccharides linked at the amide
nitrogen
of
asparagine
in the protein
confer stability on some secreted glycoproteins.
Experiments have shown that glycosylation in this case is not a strict
requirement for proper folding, but the
unglycosylated protein degrades
quickly.
Glycosylation may play a role in
cell-cell adhesion (a
mechanism employed by cells of the
immune
system), as well.
N-linked
glycosylation
N-linked glycosylation is important for the
folding of some
eukaryotic proteins.
The N-linked glycosylation process occurs in
eukaryotes and widely in archaea,
but very rarely in bacteria.
In Eukaryotes, most N-linked oligosaccharides begin with
addition of a 14-sugar precursor to the asparagine in the polypeptide
chain of the target protein.
The structure of this precursor is common
to most eukaryotes, and contains 3 glucose,
9 mannose,
and 2 N-acetylglucosamine molecules.
A complex set of reactions
attaches this branched chain to a carrier molecule called
dolichol,
and then it is transferred to the appropriate point on the polypeptide
chain as it is
translocated into the ER lumen.
There are
three major classes of
N-linked saccharides
resulting from this core:
high-mannose oligosaccharides, complex
oligosaccharides and
hybrid oligosaccharides.[2]
- High-mannose is, in essence, just two N-acetylglucosamines
with many mannose residues, often almost as many as are seen in the
precursor oligosaccharides before it is attached to the protein.
- Complex oligosaccharides are so named because they can contain
almost any number of the other types of saccharides, including more than
the original two N-acetylglucosamines.
Proteins can be glycosylated by both types of oligosaccharides on
different portions of the protein. Whether an oligosaccharide is
high-mannose or complex is thought to depend on its accessibility to
saccharide-modifying proteins in the
Golgi.
If the saccharide is relatively inaccessible, it
will most likely stay in its original high-mannose form.
If it is
accessible, then it is likely that many of the mannose residues will be
cleaved off and the saccharide will be further modified by the addition
of other types of group as discussed above.
The
oligosaccharide chain is attached by
oligosaccharyltransferase to
asparagine
occurring in the tri
peptide sequence
Asn-X-
Ser or
Asn-X-
Thr
where X could be any
amino acid except
Pro.
This sequence is known as a glycosylation
sequon.
After attachment, once the protein is correctly folded, the three
glucose residues are removed from the chain and the protein is available
for
export from the ER.
The
glycoprotein thus formed is then
transported to the Golgi where removal of further mannose residues may
take place.
However, glycosylation itself does not seem to be as
necessary for correct transport targeting of the protein, as one might
think. Studies involving drugs that block certain steps in
glycosylation, or mutant cells deficient in a glycosylation enzyme,
still produce otherwise-structurally-normal proteins that are correctly
targeted, and this interference does not seem to interfere severely with
the viability of the cells.
Mature glycoproteins may contain a variety
of oligomannose N-linked oligosaccharides containing between 5
and 9 mannose residues. Further removal of mannose residues leads to a
'core' structure containing 3 mannose,
and 2 N-acetylglucosamine residues, which may then be elongated
with a variety of different monosaccharides including galactose,
N-acetylglucosamine,
N-acetylgalactosamine, fucose and
sialic
acid.
GalNAc, glucose, and rhamnose linked to asparagines have been
observed as well, although mostly in less complex organisms or bacteria.
Glucose linked to the guanidinium group of arginine in sweet corn
amyelogenin is the only reported example of N-linked
glycosylation on an amino acid other than asparagine.
O-linked
glycosylation
O-N-acetylgalactosamine
(O-GalNAc)
O-linked glycosylation occurs at a
later stage during protein
processing, probably in the
Golgi apparatus.
This is the addition of
N-acetyl-galactosamine to
serine or
threonine
residues by the enzyme
UDP-N-acetyl-D-galactosamine:polypeptide
N-acetylgalactosaminyltransferase (
EC 2.4.1.41), followed by other
carbohydrates (such as
galactose and
sialic
acid). This process is important for certain types of proteins such
as
proteoglycans, which involves the addition of
glycosaminoglycan chains to an initially
unglycosylated "
proteoglycan core protein." These additions are
usually serine
O-linked glycoproteins, which seem to have one of
two main functions.
One function involves
secretion to form components
of the extracellular matrix, adhering one cell
to another by
interactions between the large sugar complexes of
proteoglycans.
The other main function is to act as a
component of
mucosal secretions, and it is the high concentration of
carbohydrates
that tends to give mucus its "slimy" feel.
Proteins that circulate in
the blood are not normally
O-glycosylated, with the exception of
IgA1
and
IgD (two types of antibody) and
C1-inhibitor.
The glycoproteins are:
gB (VP7 and VP8.5)
gC (VP8)
gD (VP17 and VP18)
gE (VP12.3 and VP12.6)
gG
gH
gI
gK
gL
gM
maybe:
gJ (Us5)
gN (Ul49.5)
Virion envelopes also contain at least two and possibly more nonglycosylated intrinsic membrane proteins
