title: Distinct Pores for Peroxisomal Import of PTS1 and PTS2 Proteins.
abstract: Two peroxisomal targeting signals, PTS1 and PTS2, recognized by cytosolic receptors Pex5 and cooperating Pex7/Pex18, direct folded proteins to the peroxisomal matrix. A pore consisting of the PTS1 receptor Pex5 and the docking protein Pex14 imports PTS1 proteins. We identified a distinct PTS2-specific pore, which contains the PTS2 co-receptor Pex18 and the Pex14/Pex17-docking complex as major constituents. The estimated maximal pore size of ∼ 4.7 nm is large enough to allow import of folded PTS2 proteins. PTS2 cargo proteins modulate complex gating, open probability, and subconductance states of the pore. While the PTS1 channel is transiently activated by arriving receptor-cargo complexes, the reconstituted PTS2 channel is constitutively present in an open state. However, the cargo-loaded PTS2 channel is largely impermeable to solutes and ions. Our results demonstrate that import of PTS1 and PTS2 proteins does not converge at the peroxisomal membrane as previously anticipated but is performed by distinct pores.
authors.affiliation: Biophysik, Fachbereich Biologie/Chemie, Universität Osnabrück, 49069 Osnabrück, Germany.
authors.forename: Malayko
authors.initials: M
authors.lastname: Montilla-Martinez
authors.affiliation: Institut für Biochemie und Pathobiochemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Beck
authors.affiliation: Institut für Biochemie und Pathobiochemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Klümper
authors.affiliation: Institut für Zelluläre Biochemie, Universitätsmedizin Göttingen, 37073 Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meinecke
authors.affiliation: Institut für Biochemie und Pathobiochemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schliebs
authors.affiliation: Biophysik, Fachbereich Biologie/Chemie, Universität Osnabrück, 49069 Osnabrück, Germany; MOLIFE Research Center, Jacobs University Bremen, 28759 Bremen, Germany. Electronic address: ri.wagner@jacobs-university.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Institut für Biochemie und Pathobiochemie, Ruhr-Universität Bochum, 44780 Bochum, Germany. Electronic address: ralf.erdmann@rub.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
mesh_terms: D008565:Membrane Proteins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012441:Saccharomyces cerevisiae
chemical_list: D008565:Membrane Proteins; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear