The type-2 peroxisomal targeting signal

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1867; no. 2; p. 118609
• Main Author: Kunze, Markus
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2020
• Subjects: Amino Acid Motifs; Chondrodysplasia Punctata, Rhizomelic - metabolism; Chondrodysplasia Punctata, Rhizomelic - pathology; Evolution; Humans; Membrane Proteins - metabolism; Peptide recognition; Peroxisomal Targeting Signal 2 Receptor - chemistry; Peroxisomal Targeting Signal 2 Receptor - genetics; Peroxisomal Targeting Signal 2 Receptor - metabolism; Peroxisomes; Peroxisomes - metabolism; Protein Domains; Protein Structure, Quaternary; Protein Transport; PTS2; Targeting signals; PEX; PTS2; PMP; RD; Peroxisomes; PBD; Peptide recognition; TPR; Evolution; Targeting signals; RCDP; ZSS; Protein transport
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2019.118609

The type-2 peroxisomal targeting signal (PTS2) is one of two peptide motifs destining soluble proteins for peroxisomes. This signal acts as amphiphilic α-helix exposing the side chains of all conserved residues to the same side. PTS2 motifs are recognized by a bipartite protein complex consisting of the receptor PEX7 and a co-receptor. Cargo-loaded receptor complexes are translocated across the peroxisomal membrane by a transient pore and inside peroxisomes, cargo proteins are released and processed in many, but not all species. The components of the bipartite receptor are re-exported into the cytosol by a ubiquitin-mediated and ATP-driven export mechanism. Structurally, PTS2 motifs resemble other N-terminal targeting signals, whereas the functional relation to the second peroxisomal targeting signal (PTS1) is unclear. Although only a few PTS2-carrying proteins are known in humans, subjects lacking a functional import mechanism for these proteins suffer from the severe inherited disease rhizomelic chondrodysplasia punctata. •Two types of targeting signals, PTS1 and PTS2, destine proteins for peroxisomes.•PTS2 motifs are α-helical peptides recognized by a bipartite receptor complex.•PTS2 resembles other N-terminal targeting signals, but import mechanisms differ.•In humans, inactivation of PTS2-mediated import causes a severe inherited disease.