title: Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor PEX7.
abstract: The import of a subset of peroxisomal matrix proteins is mediated by the peroxisomal targeting signal 2 (PTS2). The results of our sequence and physical property analysis of known PTS2 signals and of a mutational study of the least characterized amino acids of a canonical PTS2 motif indicate that PTS2 forms an amphipathic helix accumulating all conserved residues on one side. Three-dimensional structural modeling of the PTS2 receptor PEX7 reveals a groove with an evolutionarily conserved charge distribution complementary to PTS2 signals. Mammalian two-hybrid assays and cross-complementation of a mutation in PTS2 by a compensatory mutation in PEX7 confirm the interaction site. An unstructured linker region separates the PTS2 signal from the core protein. This additional information on PTS2 signals was used to generate a PTS2 prediction algorithm that enabled us to identify novel PTS2 signals within human proteins and to describe KChIP4 as a novel peroxisomal protein.
authors: Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria.
authors: Markus
authors: M
authors: Kunze
authors: Georg
authors: G
authors: Neuberger
authors: Sebastian
authors: S
authors: Maurer-Stroh
authors: Jianmin
authors: J
authors: Ma
authors: Thomas
authors: T
authors: Eck
authors: Nancy
authors: N
authors: Braverman
authors: Johannes A
authors: JA
authors: Schmid
authors: Frank
authors: F
authors: Eisenhaber
authors: Johannes
authors: J
authors: Berger
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics*; D000074437:Peroxisomal Targeting Signal 2 Receptor; D020675:Peroxisomes / Q000235:genetics* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D017433:Protein Structure, Secondary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism
chemical_list: D051605:Kv Channel-Interacting Proteins; C000614269:PEX7 protein, human; D000074437:Peroxisomal Targeting Signal 2 Receptor; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear