title: Motif refinement of the peroxisomal targeting signal 1 and evaluation of taxon-specific differences.
abstract: Eukaryote peroxisomes, plant glyoxysomes and trypanosomal glycosomes belong to the microbody family of organelles that compartmentalise a variety of biochemical processes. The interaction between the PTS1 signal and its cognate receptor Pex5 initiates the major import mechanism for proteins into the matrix of these organelles. Relying on the analysis of amino acid sequence variability of known PTS1-targeted proteins and PTS1-containing peptides that interact with Pex5 in the yeast two-hybrid assay, on binding site studies of the Pex5-ligand complex crystal structure, 3D models and sequences of Pex5 proteins from various taxa, we derived the requirements for a C-terminal amino acid sequence to interact productively with Pex5. We found evidence that, at least the 12 C-terminal residues of a given substrate protein are implicated in PTS1 signal recognition. This motif can be structurally and functionally divided into three regions: (i) the C-terminal tripeptide, (ii) a region interacting with the surface of Pex5 (about four residues further upstream), and (iii) a polar, solvent-accessible and unstructured region with linker function (the remaining five residues). Specificity differences are confined to taxonomic subgroups (metazoa and fungi) and are connected with amino acid type preferences in region 1 and deviating hydrophobicity patterns in region 2.
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria. neuberger@imp.univie.ac.at
authors.forename: Georg
authors.initials: G
authors.lastname: Neuberger
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maurer-Stroh
authors.forename: Birgit
authors.initials: B
authors.lastname: Eisenhaber
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartig
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000828:Animal Population Groups; D000818:Animals; D001665:Binding Sites; D005658:Fungi; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013045:Species Specificity
chemical_list: D008024:Ligands; D009842:Oligopeptides; C000614264:PEX5 protein, human; D000074435:Peroxisome-Targeting Signal 1 Receptor; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear; D012997:Solvents