SerLysLeu

SerLysLeu, commonly written as Ser-Lys-Leu and abbreviated SKL, is the canonical C-terminal tripeptide Serine–Lysine–Leucine that serves as the peroxisomal targeting signal 1 (PTS1) in many eukaryotic proteins. This short motif is typically located at the extreme C-terminus of peroxisomal matrix enzymes and other peroxisomal residents, directing them to the peroxisome.

Mechanism: The SKL motif is recognized by the cytosolic receptor Pex5, which binds cargo bearing the PTS1 and ferries it to the peroxisome membrane. Through a docking and translocation machinery, the protein is imported into the peroxisome lumen, where the tag can be removed or simply mark the protein as peroxisomal. Pex5 is recycled for reuse.

Conservation and variants: SKL is the strongest PTS1 signal, but related tripeptides such as SRL or ARL can function in many organisms, and broader consensus motifs accommodate additional residues. The efficiency of targeting depends on sequence context and protein folding.

Applications: In molecular biology and biotechnology, the SKL tag is used to redirect recombinant proteins to peroxisomes, enabling studies of peroxisomal metabolism or compartmentalized enzyme activities. Conversely, loss or mutation of the C-terminal tripeptide often mislocalizes proteins to the cytosol or other compartments.

See also: peroxisome, peroxisomal targeting signal, PTS1, Pex5.