Page 239 - Color Atlas of Biochemistry

230 Organelles

Protein synthesis and maturation all plasma proteins with the exception of al-
bumin are glycosylated. Together with glyco-
lipids, numerous glycoproteins on the cell
A. Protein synthesis in the rER
surface form the glycocalyx. Inside the ER,
With all proteins, protein biosynthesis the carbohydrate parts of the glycoproteins
(Translation; for details, see p. 250) starts on are cotranslationally transferred to the grow-
free ribosomes in the cytoplasm (1). Proteins ing chain, and are then converted into their
that are exported out of the cell or into lyso- final form while passing through the ER and
somes, and membrane proteins of the ER and Golgi apparatus.
the plasma membrane, carry a signal peptide N-bound oligosaccharides (see p. 44) are
for the ER at their N-terminus. This is a section always bound to the acid-amide group of as-
of 15–60 amino acids in which one or two paragine residues. If a glycosylation sequence
strongly basic residues (Lys, Arg) near the N- (–Asn–X–Ser(Thr)–, where X can be any
terminus are followed by a strongly hydro- amino acid) appears in the growing peptide
phobic sequence of 10–15 residues (see chain, then a transglycosylase in the ER mem-
p. 228). brane [1] transfers a previously produced core
As soon as the signal peptide (red) appears oligosaccharide consisting of 14 hexose
on the surface of the ribosome (2), an RNA- residues en-bloc from the carrier molecule
containing signal recognition particle (SRP, dolichol diphosphate to the peptide.
green) binds to the sequence and initially Dolichol is a long-chain isoprenoid (see
interrupts translation (3). The SRP then binds p. 52) consisting of 10–20 isoprene units,
to an SRP receptor in the rER membrane, and whichis embedded inthe ER membrane. A
in this way attaches the ribosome to the ER hydroxyl group at the end of the molecule is
(4). After this, the SRP dissociates from the bound to diphosphate, on which the nuclear
signal peptide and from the SRP receptor oligosaccharide is built up in an extended
and is available again for step 3. This ender- reaction sequence (not shown here in detail).
gonic process is driven by GTP hydrolysis (5). The core structure consists of two residues of
Translation now resumes. The remainder of N-acetylglucosamine (GlcNAc), a branched
the protein, still unfolded, is gradually intro- group of nine mannose residues (Man) and
duced into a channel (the translocon)inthe three terminal glucose resides (Glc).
lumen of the rER (6), where a signal peptidase As the proprotein passes through the ER,
located in the inner ER membrane cleaves the glycosidases [2] removethe glucoseresidues
signal peptide while translation is still taking completely and the mannoses partially
place (7). This converts the preprotein into a (“trimming”), thereby producing the man-
proprotein,from which thematureprotein nose-rich type of oligosaccharide residues.
finally arises after additional post-transla- Subsequently, various glycosyltransferases [3]
tional modifications (8) inthe ER and inthe transfer additional monosaccharides (e. g.,
Golgi apparatus. GlcNAc,galactose,fucose, andN-acetylneura-
If the growing polypeptide contains a stop- minic acid; see p. 38) to the mannose-rich
transfer signal (see p. 228), then this hydro- intermediate and thereby produce the com-
phobic section of the chain remains stuck in plex type of oligosaccharide. The structure of
themembraneoutside the translocon, andan the final oligosaccharide depends on the type
integral membrane protein arises. In the and activity of the glycosyltransferases pre-
course of translation, an additional signal se- sent in the ER of the cell concerned, and is
quence can re-start the transfer of the chain therefore genetically determined (although
through the translocon. Several repetitions of indirectly).
this process produce integral membrane pro-
teins with several transmembrane helices
(see p. 214).

B. Protein glycosylation
Most extracellular proteins contain covalently
bound oligosaccharide residues. For example,

Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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