signal sequence followed by a stop-transfer sequence, followed by a start-transfer sequence,
followed by another stop transfer sequence o N terminus in ER lumen, C terminus in cytosol
Solution
N terminal ER signal is a sequence that that codes for an 8-14 hydrophobic amino acid signal
sequence of growing polypeptide. It targets the protein to the ER. SRP binds to SRP receptor
present on cytosolic surface of ER membrane. It cleaves after the protein is transferred to ER
membrane. As a result, the SRP-ribosome complex comes near a protein translocator. The SRP
and SRP receptor are released, transferring the growing polypeptide chain across the membrane.
This N terminal signal sequence is followed by an 8-14 hydrophobic stop transfer sequence,
which is a membrane-closing domain. It remains in the membrane. Encountering this stop signal
causes disassembly of the translocation channel. This peptide is not cleaved and the translation
continues in cytoplasm. This stop-transfer signal anchors the protein in the membrane.
The stop signal is followed by an internal start signal again which binds to signal recognition
particle (SRP) to initiate transfer. A second translocation assembly is opened in the membrane. It
is followed by another stop transfer signal. As a result, the polypeptide chain is released.
N terminus signal sequence will target the N terminus end to the ER lumen. The stop signal will
anchor it. Here, there is disassembly of the translocation channel. The C terminus is in cytosol.
Protein synthesis will continue and when the start signal is encountered, another translocation
signal is opened. Start signal will embed the protein in membrane. C terminus now comes in the
ER lumen. Encountering the stop signal the polypeptide is now again anchored in membrane.
The protein chain is released, with C terminus now in cytosol.
The N terminus is therefore in the ER lumen and the C terminus is in cytosol. It is a double
membrane pass protein with N terminus in ER lumen and C terminus in cytosol.