Peroxisomes, protein targeting signals

Olivier, L.M., Krisans, S.K. 2000. Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. Biochim. Biophys. Acta 1529 89-102. 

Both the integral membrane proteins of peroxisomes as well as the peroxisomal matrix proteins are synthesised on free polyribosomes and are specifically targeted to peroxisomes via dedicated peroxisomal targeting signals. The biogenesis of peroxisomes follows a sequential pattern, which involves first the insertion of peroxisomal membrane proteins into the membrane of the pre-peroxisomal structure, derived from the endoplasmic reticulum, followed by insertion of the various matrix proteins. 

Neuberger G, Maurer-Stroh S, Eisenhaber B, Hartig A, Eisen-haber F. 2003. Prediction of peroxisomal targeting signal 1 containing proteins from amino acid sequence. J Mol Biol 328 581-592. 

Proteins targeted to cytoplasmic compartments contain a variety of signaling sequences which direct them to the cytoplasmic face of membranes, mitochondria, the nucleus, or peroxisomes. 

Proteins destined for peroxisomes have their own targeting signals. One of these (PTSl) is the sequence SKL at the C terminus. A second signal (PTS2) is an N-terminal nonapeptide (R / K)(L / V/1) X5(H /Q)... 

Recently sequences which can route proteins to peroxisomes have been identified (91). Firefly luciferase, a peroxisomal protein, contains a C-terminal serine-lysine-leucine which was shown to be critical for proper targeting. Indeed, most peroxisomal proteins analyzed thus far show similar sequences at their C-terminus a minority of proteins apparently utilize amino-terminal or internal signal sequences (92,93). 

The import of proteins into peroxisomes is directed by peroxisomal targeting signals (PTSs) (Subramani, 1992). A carboxy-terminal tripeptide with the sequence SKL (in the one-letter amino acid code) represents a prototype PTS. Crosslinking of a peptide ending in SKL to a carrier protein creates an artificial substrate for the peroxisomal import machinery (Walton et al., 1992). 

Walton, P. A., Gould, S. J., Feramisco, J. R., and Subramani, S. (1992) Transport of microin-jected proteins into peroxisomes of mammalian cells Inability of Zellweger cell lines to import proteins with the SKL tripeptide peroxisomal targeting signal. Mol. Cell. Biol. 12,... 

The fact that proteins destined for peroxisomes are synthesised on free polyribosomes implies that these proteins must possess specific signals to direct them to peroxisomes. Two of such Peroxisome Targeting Signals (PTS) have been identified. The first PTS involves a carboxyterminal tripeptide of the sequence serine-lysine-leucine (SKL) or a variant thereof and many peroxisomal proteins contain such a PTSl. 

---