Essential Cell Biology 5th edition

Protein Sorting
509
mRNA
growing
polypeptide
chain
ER signal
sequence
ribosome
signalrecognition
particle (SRP)
SRP receptor
SRP displaced and released for reuse
protein
translocator
CYTOSOL
ER LUMEN
Figure 15–14 An ER signal sequence
and an SRP direct a ribosome to the ER
membrane. The SRP (brown) binds to both
the exposed ER signal sequence and the
ribosome, thereby slowing protein synthesis
by the ribosome. The SRP–ribosome
complex then binds to an SRP receptor
(dark blue) in the ER membrane. The SRP is
released, and the ribosome passes from the
SRP receptor to a protein translocator (light
blue) in the ER membrane. Protein synthesis
resumes, and the translocator starts to
transfer the growing polypeptide across the
lipid bilayer.
the ribosome; and (2) an SRP receptor, embedded in the ER membrane,
recognizes the SRP. Binding of an SRP to a ribosome that displays an
ER signal sequence slows protein synthesis by that ribosome until the
SRP engages with an SRP receptor on the ER. Once bound, the SRP is
released, the receptor passes the ribosome to a protein translocator in
the ER membrane, and protein synthesis recommences. The polypeptide
is then threaded across the ER
ECB5
membrane
e15.14-15.14
through a channel in the
translocator (Figure 15–14). The SRP and SRP receptor thus function as
molecular matchmakers, bringing together ribosomes that are synthesizing
proteins with an ER signal sequence and protein translocators within
the ER membrane.
In addition to directing proteins to the ER, the signal sequence—which
for soluble proteins is almost always at the N-terminus, the end synthesized
first—functions to open the protein translocator. This sequence
remains bound to the translocator, while the rest of the polypeptide chain
is threaded through the membrane as a large loop. The signal sequence
is removed by a transmembrane signal peptidase, which has an active
site facing the lumenal side of the ER membrane. The cleaved signal
sequence is then released from the protein translocator into the lipid
bilayer and rapidly degraded.
Once the C-terminus of a soluble protein has passed through the translocator,
the protein is released into the ER lumen (Figure 15–15).
QUESTION 15–3
Explain how an mRNA molecule
can remain attached to the
ER membrane while individual
ribosomes translating it are released
and rejoin the cytosolic pool of
ribosomes after each round of
translation.
Start and Stop Signals Determine the Arrangement of a
Transmembrane Protein in the Lipid Bilayer
Not all proteins made by ER-bound ribosomes are released into the ER
lumen. Some remain embedded in the ER membrane as transmembrane
proteins. The translocation process for such proteins is more complicated
ER signal
sequence
protein
translocator
growing polypeptide chain
emerging from ribosome
closed protein
translocator
signal
peptidase
cleaved signal
peptide
NH 2 CYTOSOL
ER LUMEN
NH 2
COOH
mature soluble
protein in ER lumen
Figure 15–15 A soluble protein crosses
the ER membrane and enters the lumen.
The protein translocator binds the signal
sequence and threads the rest of the
polypeptide across the lipid bilayer as a
loop. At some point during the translocation
process, the signal peptide is cleaved
from the growing protein by a signal
peptidase (yellow). This cleaved signal
sequence is ejected into the bilayer, where
it is degraded. Once protein synthesis is
complete, the translocated polypeptide is
released as a soluble protein into the ER
lumen, and the protein translocator closes.
The membrane-bound ribosome is omitted
from this and the following two figures for
clarity.