title: The difference in recognition of terminal tripeptides as peroxisomal targeting signal 1 between yeast and human is due to different affinities of their receptor Pex5p to the cognate signal and to residues adjacent to it.
abstract: Pex5p is the receptor for the peroxisomal targeting signal 1 (PTS1) that consists of a C-terminal tripeptide (consensus (S/A/C)(K/R/H)(L/M)). Hexadecapeptides recognized by Pex5p from Homo sapiens and Saccharomyces cerevisiae were identified by screening a two-hybrid peptide library, and the targeting ability of the peptides was demonstrated using the green fluorescent protein as reporter. The PTS1 receptors recognized in a species-specific manner a broad range of C-terminal tripeptides, and these are reported herein. In addition, residues upstream of the tripeptide influenced the strength of the interaction in the two-hybrid system as well as in an in vitro competition assay. In peptides interacting with the human protein, hydrophobic residues were found with high frequency especially at positions -2 and -5, whereas peptides interacting with S. cerevisiae Pex5p were more hydrophilic and frequently contained arginine at position -2. In instances where the terminal tripeptide deviated from the consensus, upstream residues exerted a greater influence on the ability of the hexadecapeptides to bind Pex5p.
authors.affiliation: Institut fuer Biochemie und Molekulare Zellbiologie der Universitaet Wien and Ludwig Boltzmann-Forschungsstelle fuer Biochemie, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Wien, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Lametschwandtner
authors.forename: C
authors.initials: C
authors.lastname: Brocard
authors.forename: M
authors.initials: M
authors.lastname: Fransen
authors.forename: P
authors.initials: P
authors.lastname: Van Veldhoven
authors.forename: J
authors.initials: J
authors.lastname: Berger
authors.forename: A
authors.initials: A
authors.lastname: Hartig
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D000074435:Peroxisome-Targeting Signal 1 Receptor; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D009842:Oligopeptides; D000074435:Peroxisome-Targeting Signal 1 Receptor; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear