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Pts2Edit

PTS2, or peroxisomal targeting signal type 2, is a short amino acid sequence that directs certain proteins to the peroxisome. This signal is typically located at the N-terminus of cargo proteins and is recognized by the cytosolic receptor Pex7 before being directed to the peroxisomal import machinery. Along with the more common PTS1 signal, PTS2 helps ensure that a wide range of enzymes reach the peroxisome to carry out essential metabolic tasks.

Overview

  • The PTS2 signal is a nonapeptide with a general motif that is often described as RL-x5-HL, positioned near the start of the protein. While the exact sequence can vary across species, the basic pattern remains a recognizable cue for the import system. peroxisomal targeting signal 2.
  • Cargo proteins bearing PTS2 are recognized by the cytosolic receptor Pex7 and are then delivered to the peroxisomal membrane, where a docking complex including Pex14 and related components facilitates translocation of the protein into the peroxisomal matrix. In some organisms, co-receptors such as Pex18 and Pex21 assist PTS2 import, illustrating evolutionary variation in the import machinery. Pex7.
  • The PTS2 pathway operates alongside the PTS1 pathway; many peroxisomal matrix proteins can be targeted by either signal, providing redundancy that helps safeguard essential peroxisomal functions such as fatty acid β-oxidation and reactive oxygen species detoxification. For background on the broader targeting system, see peroxisome and peroxisomal targeting signal 1.

Molecular recognition and transport

  • The recognition of PTS2 occurs in the cytosol, where Pex7 binds the signal-bearing cargo. The PTS2–Pex7 complex interacts with membrane-associated docking factors, enabling the cargo to be threaded into the peroxisome via the import apparatus. This process is sometimes described as an importomer that coordinates receptor cycling and matrix protein delivery. Pex7, Pex14.
  • The exact details of how PTS2-containing proteins are released into the matrix after docking can differ among species, but the conserved principle remains: a dedicated receptor–co-receptor system recognizes a short N-terminal tag and shepherds the enzyme into the peroxisomal lumen. See discussions of the broader import machinery in peroxisome.

Cargoes and functional roles

  • PTS2 signals are found on a subset of peroxisomal matrix enzymes, many involved in fatty acid metabolism and other peroxisomal pathways. Notable classes include enzymes participating in β-oxidation, as well as auxiliary enzymes that support peroxisomal function. Examples and descriptions of specific PTS2 cargoes can be found in entries on relevant enzymes and metabolic pathways, such as 3-ketoacyl-CoA thiolase and beta-oxidation.
  • Some peroxisomal enzymes are dual-targeted or can use either PTS1 or PTS2, reflecting flexibility in the cellular targeting system. This redundancy helps maintain peroxisome function under conditions where one targeting route is compromised. See also discussions of dual targeting in protein targeting.

Evolution, diversity, and regulation

  • The PTS2 pathway shows variation across species, with differences in receptor composition and co-receptor assistance. In yeast, for example, co-receptors such as Pex18 and Pex21 play important roles, while in higher eukaryotes the Pex7–Pex14 axis provides the core mechanism. These differences highlight how a conserved targeting concept can be adapted to distinct cellular contexts. Pex18, Pex21.
  • Regulation of PTS2 import can respond to cellular metabolic state, organelle biogenesis, and stress conditions. Given the central role of peroxisomes in lipid metabolism and detoxification, changes in PTS2 traffic can influence overall metabolic homeostasis. See broader discussions of peroxisomal biology in peroxisome and peroxisomal biogenesis disorder.

Clinical significance and research directions

  • Defects in peroxisomal targeting can contribute to peroxisomal biogenesis disorders, in which the abundance or functionality of peroxisomes is compromised. When the PTS2 import pathway is impaired, resident enzymes may fail to reach the peroxisome, leading to metabolic disturbances. These conditions overlap with the Zellweger spectrum disorders and related peroxisomal diseases, where multiple targeting routes may be affected. See Zellweger spectrum disorder and peroxisomal biogenesis disorder for broader context.
  • Diagnostic and therapeutic research continues to clarify the contribution of PTS2-specific defects to disease phenotypes and to explore potential strategies to restore proper targeting, including modulation of the Pex7–Pex14 axis and related components. For related topics in peroxisomal pathology, consult peroxisomal biogenesis disorder.

See also