serinelysineleucine

SerineLysineLeucine, commonly abbreviated SKL, refers to the canonical C-terminal tripeptide Ser-Lys-Leu that serves as a peroxisomal targeting signal type 1 (PTS1) in many eukaryotic proteins. The SKL motif directs proteins to peroxisomes, which are organelles involved in fatty acid beta-oxidation, reactive oxygen species detoxification, and other metabolic processes. As the classical PTS1, SKL is widely used as a key determinant of peroxisomal localization across diverse species.

Mechanistically, the SKL motif is recognized by the cytosolic receptor Pex5. Binding of Pex5 to the C-terminus of a peroxisomal protein facilitates docking at the peroxisomal membrane and translocation into the organelle, a process coordinated with other peroxins such as Pex14. Peroxisomal import can accommodate folded proteins and multisubunit assemblies, and the presence of SKL is often necessary and sufficient for targeting, though the surrounding sequence context can influence efficiency and specificity.

The SKL tripeptide is highly conserved and has been a focal point in studies of peroxisome biogenesis and protein trafficking. Variants of the PTS1 sequence related to SKL can function in some organisms, and synthetic fusions attaching SKL or related motifs to proteins are routinely used in research and biotechnology to direct proteins to peroxisomes. Malfunctions in peroxisomal protein import pathways are implicated in peroxisomal biogenesis disorders, highlighting the biological importance of proper SKL-mediated targeting.