The nucleus encodes all peroxisomal proteins because peroxisomes don’t contain their own DNA or ribosomes. The cell’s nuclear DNA encodes the genes for all peroxisomal proteins (e.g., catalase, the enzyme that breaks down hydrogen peroxide). These genes are transcribed into mRNA in the nucleus. The mRNA then travels to the cytosol, where free ribosomes translate it into the protein chains (polypeptides). Specific receptors on the peroxisomal membrane then recognize and import the newly synthesized, unfolded proteins directly from the cytosol into the peroxisome, where they fold into their active form. Lets discuss in detail about this Peroxisomal Protein Targeting.
Peroxisomal Targeting Signals
After synthesis on cytosolic ribosomes, these fully formed proteins carry specific peroxisomal targeting signals (PTS1 or PTS2). Dedicated receptor proteins (peroxins) on the peroxisomal membrane then facilitate the post-translational import of the proteins into the organelle. This unique import mechanism distinguishes peroxisomes from semi-autonomous organelles like mitochondria and chloroplasts, highlighting their different evolutionary path.
Import relies on specific targeting signals and receptor proteins (peroxins, PEX proteins). Peroxisomal protein targeting involves PTS1, PTS2 signals and peroxin proteins such as PEX5, PEX7, and PEX19 that guide proteins to the peroxisome.
1. Matrix protein import via PTS1
- Most peroxisomal matrix proteins have a C-terminal tripeptide (usually Ser-Lys-Leu, SKL), called PTS1.
- This PTS1 signal is recognized by PEX5, a soluble receptor in the cytosol.
- The PEX5–cargo complex travels to the peroxisomal membrane.
- At the membrane, it docks with PEX14 (a docking factor), and the cargo is translocated into the peroxisomal matrix.
- After delivery, PEX5 is recycled back into the cytosol with the help of other peroxins and the AAA-ATPase complex (PEX1–PEX6).
2. Matrix protein import via PTS2
- A smaller set of peroxisomal proteins carry an N-terminal nonapeptide (9 amino acids), called PTS2.
- This signal is recognized by PEX7, the cytosolic receptor for PTS2.
- In many cases, PEX5 also acts as a co-receptor, helping PEX7 to dock the cargo at the peroxisomal membrane.
- Like PTS1 proteins, these PTS2 cargoes are imported inside, and receptors are recycled.
3. Peroxisomal membrane protein (PMP) targeting
- PMPs (proteins that form the peroxisomal membrane) do not use PTS1 or PTS2.
- Instead, they use PEX19, a chaperone and receptor.
- PEX19 binds PMPs in the cytosol, keeps them soluble, and delivers them to the peroxisome by interacting with PEX3 on the membrane.
- This ensures the correct insertion of PMPs into the peroxisomal membrane.
🔎 Key Peroxins Explained
PEX5
- Receptor for PTS1 proteins.
- A soluble cytosolic protein that binds SKL-tagged proteins.
- Acts as a shuttle: cytosol → peroxisomal membrane → release cargo → recycled.
- Also interacts with PEX14 (docking) and PEX13 at the membrane.
PEX7
- Receptor for PTS2 proteins (N-terminal signal).
- Works alone in yeast, but in mammals it needs PEX5 as a co-receptor to dock at the peroxisome.
- Mutations in PEX7 → defective PTS2 import → diseases like Rhizomelic Chondrodysplasia Punctata (RCDP).
PEX19
- Receptor and chaperone for peroxisomal membrane proteins (PMPs).
- Prevents PMPs from aggregating in cytosol.
- Delivers them to PEX3 on the peroxisomal membrane for insertion.
- Essential for peroxisome membrane biogenesis.
🔁 Summary of the Targeting Process
- PTS1 (C-terminal SKL) → PEX5 → PEX14 → Matrix import.
- PTS2 (N-terminal nonapeptide) → PEX7 (+PEX5 co-receptor) → PEX14 → Matrix import.
- PMPs → PEX19 → PEX3 → Insert into peroxisomal membrane.
👉 In short:
- PEX5 = PTS1 receptor (C-terminal cargo)
- PEX7 = PTS2 receptor (N-terminal cargo)
- PEX19 = Membrane protein receptor/chaperone
Summary:
Peroxisomal protein targeting is essential for the proper functioning of peroxisomes. Most matrix proteins use the PTS1 signal at the C-terminal, recognized by PEX5. A smaller group use the PTS2 signal at the N-terminal, identified by PEX7 with help from PEX5. Both signals ensure correct transport of enzymes into the peroxisomal matrix. In contrast, peroxisomal membrane proteins (PMPs) are guided by PEX19, which acts as a chaperone and receptor, delivering them to the membrane through PEX3. Together, PEX5, PEX7, and PEX19 maintain peroxisome biogenesis and metabolism. Mutations in these genes can cause severe peroxisomal disorders.
MCQs on Peroxisomal Protein Targeting
Q1. PTS1 signal sequence is located at which part of the protein?
a) N-terminal
b) C-terminal
c) Internal sequence
d) Transmembrane domain
👉 Answer: b) C-terminal
✔ Explanation: PTS1 (Peroxisomal Targeting Signal 1) is a short tripeptide sequence (usually Ser-Lys-Leu, SKL) found at the C-terminus of most peroxisomal proteins.
Q2. PTS2 sequence is recognized at which end of the protein?
a) N-terminal
b) C-terminal
c) Both ends
d) Internal non-terminal region
👉 Answer: a) N-terminal
✔ Explanation: PTS2 is a nonapeptide (9 amino acids long) present near the N-terminus of certain peroxisomal matrix proteins.
Q3. Which receptor protein recognizes the PTS1 signal sequence?
a) PEX5
b) PEX7
c) PEX13
d) PEX19
👉 Answer: a) PEX5
✔ Explanation: PEX5 is the cytosolic receptor that binds to proteins carrying the PTS1 signal and transports them to the peroxisomal membrane.
Q4. PTS2 signal is recognized by which receptor?
a) PEX5
b) PEX7
c) PEX14
d) PEX19
👉 Answer: b) PEX7
✔ Explanation: PEX7 specifically recognizes and binds to proteins carrying the PTS2 sequence.
Q5. Which peroxin acts as a docking factor on the peroxisomal membrane for PTS1-PEX5 complex?
a) PEX13
b) PEX14
c) PEX19
d) PEX26
👉 Answer: b) PEX14
✔ Explanation: PEX14 interacts with PEX5 (PTS1 receptor) at the peroxisomal membrane, allowing cargo delivery.
Q6. Which peroxisomal targeting signal is more common in human peroxisomal matrix proteins?
a) PTS1
b) PTS2
c) Both equally common
d) None
👉 Answer: a) PTS1
✔ Explanation: Most human peroxisomal matrix proteins use PTS1 (C-terminal SKL or variants); only a few use PTS2.
Q7. Mutations in PEX7 gene affect which targeting pathway?
a) PTS1 pathway
b) PTS2 pathway
c) Both PTS1 and PTS2 pathways
d) None
👉 Answer: b) PTS2 pathway
✔ Explanation: PEX7 is the receptor for PTS2 signals. Mutations in PEX7 cause disorders like Rhizomelic Chondrodysplasia Punctata (RCDP), due to defective import of PTS2 proteins.
Q8. Which of the following is NOT involved in peroxisomal matrix protein import?
a) PEX5
b) PEX7
c) PEX14
d) TIM23
👉 Answer: d) TIM23
✔ Explanation: TIM23 is a mitochondrial protein import complex, not peroxisomal.
Q9. Peroxisomal membrane proteins (PMPs) are targeted via which receptor?
a) PEX5
b) PEX7
c) PEX19
d) PEX26
👉 Answer: c) PEX19
✔ Explanation: PEX19 acts as a chaperone and receptor for peroxisomal membrane proteins (PMPs).
Q10. The “SKL” tripeptide at the C-terminal is a classic example of which peroxisomal signal?
a) PTS1
b) PTS2
c) PMP targeting signal
d) ER retention signal
👉 Answer: a) PTS1
✔ Explanation: The Ser-Lys-Leu (SKL) motif is the canonical PTS1 signal.