PTS1

PTS1, or peroxisomal targeting signal 1, is a short amino acid sequence at the extreme C-terminus of many peroxisomal matrix proteins that directs their import into peroxisomes. The most common PTS1 motif is the tripeptide Ser-Lys-Leu (SKL), but a broad range of variants can function as PTS1 with varying efficiency. A general, though not absolute, consensus pattern encompasses a small set of C-terminal residues, often described as a [S/A/C]-[K/R]-[L/M] motif, though exceptions exist.

Mechanism and function: PTS1 is recognized by the cytosolic receptor Pex5, which binds the cargo protein via its PTS1 motif. The Pex5-cargo complex docks at the peroxisomal membrane through interactions with docking factors such as Pex13 and Pex14, and the cargo is translocated into the peroxisomal lumen. After delivery, Pex5 is recycled back to the cytosol by the ATPases Pex1 and Pex6 to engage new cargo.

Biological significance: The PTS1 pathway is essential for importing most peroxisomal matrix enzymes, including those involved in fatty acid beta-oxidation and reactive oxygen species detoxification. Disruptions in PTS1 recognition or transport can contribute to peroxisomal biogenesis disorders, such as Zellweger spectrum disorders, reflecting the importance of proper peroxisomal protein targeting.

Applications: In research and biotechnology, appending a PTS1 sequence to a protein is a common method to target it to peroxisomes for localization studies or metabolic engineering.

Related signals: PTS2 is an alternate peroxisomal targeting signal located at the N-terminus and recognized by Pex7, illustrating multiple import routes for peroxisomal proteins.