Signal peptide and signal recognition particle: targeting to the rough ER
The signal recognition particle binds a hydrophobic (water-hating) signal sequence at the start of a new chain and takes the ribosome to the rough endoplasmic reticulum (ER) during translation.
Remember
A hydrophobic signal peptide at the N-terminus (the start of the chain), also called the signal sequence, is recognised by the signal recognition particle during translation, which takes the ribosome to the rough ER so that the chain is fed in as it is made.
Memory aid
SRP is the courier, the receptor is the door, and without the door the parcel stays outside.
Think of a delivery: SRP brings the ribosome, the SRP receptor is the door at the ER, and if the door does not work the protein is left in the cytosol.
Proteins made for secretion most commonly carry an address label at the start of the chain. This signal sequence is a short run of mainly hydrophobic (water-avoiding) amino acids at the N-terminus (the start of the chain, which is the first part made).
Because it is made first, the signal sequence appears as soon as it leaves the ribosome. The signal recognition particle (SRP, a protein-RNA complex) recognises and binds it, slows elongation (the lengthening of the chain), and escorts the whole ribosome and growing chain to the rough ER. This happens during translation, so it is called co-translational targeting.
At the ER membrane, the SRP binds its receptor. Hydrolysing GTP (splitting this energy-carrying molecule with water) completes the handover of the chain to a protein channel and frees the SRP to collect another ribosome. The ribosome carries on translating, and the growing chain is fed into the lumen (the space inside the ER) in a secreted protein, or into the membrane in a membrane protein. Later, the enzyme signal peptidase usually removes the signal sequence.
Without the signal sequence, the SRP has nothing to recognise. The ribosome stays free in the cytosol (the fluid of the cell), and the protein is finished there. Proteins for the nucleus and mitochondria are made on free ribosomes and delivered after synthesis, so timing helps to tell the routes apart.
Key facts
- Address label
- A mainly hydrophobic run of amino acids at the N-terminus marks a secreted protein for the ER.
- First event
- SRP binding the signal sequence as it emerges from the ribosome is what starts targeting.
- SRP pause
- SRP slows elongation, which gives the ribosome time to be delivered to the ER, rather than stopping translation permanently.
- Two recognition steps
- Targeting needs SRP to recognise the signal sequence and the SRP-ribosome complex to engage the SRP receptor.
- GTP switch
- Hydrolysis of GTP in the SRP-receptor pair releases SRP and completes the handover of the chain to the translocation channel (the protein channel that moves the chain across the ER membrane).
- No signal sequence
- The SRP has nothing to recognise, so the protein is made on a free ribosome and stays in the cytosol.
Exam traps
- Signal peptidase does not start targeting, because it acts only after the chain has entered the ER lumen, which makes it a late step.
- SRP does not stop translation permanently, and the pause is not a signal for degrading the ribosome: it gives the ribosome time to be delivered to the ER.
- A secreted protein that lacks its signal sequence is not inserted into the ER membrane by hydrophobic regions added after translation, because the hydrophobic signal sequence is part of the polypeptide chain itself and is not added later.
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