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Unraveling of the Structure and Function of Peroxisomal Protein Import Machineries

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Proteomics of Peroxisomes

Part of the book series: Subcellular Biochemistry ((SCBI,volume 89))

Abstract

Peroxisomes are dynamic organelles of eukaryotic cells performing a wide range of functions including fatty acid oxidation, peroxide detoxification and ether-lipid synthesis in mammals. Peroxisomes lack their own DNA and therefore have to import proteins post-translationally. Peroxisomes can import folded, co-factor bound and even oligomeric proteins. The involvement of cycling receptors is a special feature of peroxisomal protein import. Complex machineries of peroxin (PEX) proteins mediate peroxisomal matrix and membrane protein import. Identification of PEX genes was dominated by forward genetic techniques in the early 90s. However, recent developments in proteomic techniques has revolutionized the detailed characterization of peroxisomal protein import. Here, we summarize the current knowledge on peroxisomal protein import with emphasis on the contribution of proteomic approaches to our understanding of the composition and function of the peroxisomal protein import machineries.

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Abbreviations

AAA:

ATPase Associated with diverse cellular Activities

DUBs:

De-ubiquitinating enzymes

mPTS:

membrane Peroxisome Targeting Signal

PBDs:

Peroxisome Biogenesis Disorders

PEX:

Peroxin

PMPs:

Peroxisomal Membrane Proteins

PTS:

Peroxisome Targeting Signal

RING:

Really Interesting New Gene

SH3:

Src Homology 3

TEV:

Tobacco Etch Virus protease

TPA:

TEV cleavage site—protein A

TPR:

Tetratrico-Peptide Repeat

References

  • Agne B, Meindl NM, Niederhoff K, Einwachter H, Rehling P, Sickmann A, Meyer HE, Girzalsky W, Kunau WH (2003) Pex8p: an intraperoxisomal organizer of the peroxisomal import machinery. Mol Cell 11:635–646

    Article  CAS  PubMed  Google Scholar 

  • Agrawal G, Subramani S (2016) De novo peroxisome biogenesis: evolving concepts and conundrums. Biochim Biophys Acta 1863:892–901

    Article  CAS  PubMed  Google Scholar 

  • Albertini M, Rehling P, Erdmann R, Girzalsky W, Kiel JA, Veenhuis M, Kunau WH (1997) Pex14p, a peroxisomal membrane protein binding both receptors of the two PTS-dependent import pathways. Cell 89:83–92

    Article  CAS  PubMed  Google Scholar 

  • Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423:181–185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bottger G, Barnett P, Klein AT, Kragt A, Tabak HF, Distel B (2000) Saccharomyces cerevisiae PTS1 receptor Pex5p interacts with the SH3 domain of the peroxisomal membrane protein Pex13p in an unconventional, non-PXXP-related manner. Mol Biol Cell 11:3963–3976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brennand A, Rigden DJ, Michels PA (2012) Trypanosomes contain two highly different isoforms of peroxin PEX13 involved in glycosome biogenesis. FEBS Lett 586:1765–1771

    Article  CAS  PubMed  Google Scholar 

  • Brocard C, Hartig A (2006) Peroxisome targeting signal 1: is it really a simple tripeptide? Biochim Biophys Acta 1763:1565–1573

    Article  CAS  PubMed  Google Scholar 

  • Brzovic PS, Klevit RE (2006) Ubiquitin transfer from the E2 perspective: why is UbcH5 so promiscuous? Cell Cycle 5:2867–2873

    Article  CAS  PubMed  Google Scholar 

  • Chan A, Schummer A, Fischer S, Schröter T, Cruz-Zaragoza LD, Bender J, Drepper F, Oeljeklaus S, Kunau WH, Girzalsky W, Warscheid B, Erdmann R (2016) Pex17p-dependent assembly of Pex14p/Dyn2p-subcomplexes of the peroxisomal protein import machinery. Eur J Cell Biol 95:585–597

    Article  CAS  PubMed  Google Scholar 

  • Chang J, Tower RJ, Lancaster DL, Rachubinski RA (2013) Dynein light chain interaction with the peroxisomal import docking complex modulates peroxisome biogenesis in yeast. J Cell Sci 126:4698–4706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ciniawsky S, Grimm I, Saffian D, Girzalsky W, Erdmann R, Wendler P (2015) Molecular snapshots of the Pex1/6 AAA+ complex in action. Nat Commun 6:7331

    Article  CAS  PubMed  Google Scholar 

  • Colasante C, Voncken F, Manful T, Ruppert T, Tielens AGM, van Hellemond JJ, Clayton C (2013) Proteins and lipids of glycosomal membranes from Leishmania tarentolae and Trypanosoma brucei. F1000Res 2:27

    Google Scholar 

  • Corpas FJ, Palma JM, del Río LA (1993) Evidence for the presence of proteolytic activity in peroxisomes. Eur J Cell Biol 61:81–85

    CAS  PubMed  Google Scholar 

  • Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Mäser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann R, Sattler M, Popowicz GM (2017) Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Science 355:1416–1420

    Article  CAS  PubMed  Google Scholar 

  • Debelyy MO, Platta HW, Saffian D, Hensel A, Thoms S, Meyer HE, Warscheid B, Girzalsky W, Erdmann R (2011) Ubp15p, a ubiquitin hydrolase associated with the peroxisomal export machinery. J Biol Chem 286:28223–28234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Distefano S, Palma JM, Gómez M, del Río LA (1997) Characterization of endoproteases from plant peroxisomes. Biochem J 327:399–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Distefano S, Palma JM, McCarthy I, del Río LA (1999) Proteolytic cleavage of plant proteins by peroxisomal endoproteases from senescent pea leaves. Planta 209:308–313

    Article  CAS  PubMed  Google Scholar 

  • Douangamath A, Filipp FV, Klein AT, Barnett P, Zou P, Voorn-Brouwer T, Vega MC, Mayans OM, Sattler M, Distel B, Wilmanns M (2002) Topography for independent binding of alpha-helical and PPII-helical ligands to a peroxisomal SH3 domain. Mol Cell 10:1007–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Effelsberg D, Cruz-Zaragoza LD, Tonillo J, Schliebs W, Erdmann R (2015) Role of Pex21p for piggyback import of Gpd1p and Pnc1p into peroxisomes of Saccharomyces cerevisiae. J Biol Chem 290:25333–25342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Magraoui F, Baumer BE, Platta HW, Baumann JS, Girzalsky W, Erdmann R (2012) The RING-type ubiquitin ligases Pex2p, Pex10p and Pex12p form a heteromeric complex that displays enhanced activity in an ubiquitin conjugating enzyme-selective manner. FEBS J 279:2060–2070

    Article  PubMed  CAS  Google Scholar 

  • El Magraoui F, Brinkmeier R, Schrotter A, Girzalsky W, Muller T, Marcus K, Meyer HE, Erdmann R, Platta HW (2013) Distinct ubiquitination cascades act on the peroxisomal targeting signal type 2 co-receptor Pex18p. Traffic 14:1290–1301

    Article  PubMed  CAS  Google Scholar 

  • Emmanouilidis L, Schutz U, Tripsianes K, Madl T, Radke J, Rucktaschel R, Wilmanns M, Schliebs W, Erdmann R, Sattler M (2017) Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19. Nat Commun 8:14635

    Article  PubMed  PubMed Central  Google Scholar 

  • Erdmann R, Blobel G (1995) Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p. J Cell Biol 128:509–523

    Article  CAS  PubMed  Google Scholar 

  • Erdmann R, Schliebs W (2005) Peroxisomal matrix protein import: the transient pore model. Nat Rev Mol Cell Biol 6:738–742

    Article  CAS  PubMed  Google Scholar 

  • Erdmann R, Veenhuis M, Mertens D, Kunau WH (1989) Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 86:5419–5423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang Y, Morrell JC, Jones JM, Gould SJ (2004) PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins. J Cell Biol 164:863–875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farre JC, Carolino K, Stasyk OV, Stasyk OG, Hodzic Z, Agrawal G, Till A, Proietto M, Cregg J, Sibirny AA, Subramani S (2017) A new yeast peroxin, Pex36, a functional homolog of mammalian PEX16, functions in the ER-to-peroxisome traffic of peroxisomal membrane proteins. J Mol Biol 429:3743–3762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flynn CR, Mullen RT, Trelease RN (1998) Mutational analyses of a type 2 peroxisomal targeting signal that is capable of directing oligomeric protein import into tobacco BY-2 glyoxysomes. Plant J 16:709–720

    Article  CAS  PubMed  Google Scholar 

  • Fransen M, Vastiau I, Brees C, Brys V, Mannaerts GP, Van Veldhoven PP (2004) Potential role for Pex19p in assembly of PTS-receptor docking complexes. J Biol Chem 279:12615–12624

    Article  CAS  PubMed  Google Scholar 

  • Freitas MO, Francisco T, Rodrigues TA, Alencastre IS, Pinto MP, Grou CP, Carvalho AF, Fransen M, Sa-Miranda C, Azevedo JE (2011) PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14. J Biol Chem 286:40509–40519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Girzalsky W, Rehling P, Stein K, Kipper J, Blank L, Kunau WH, Erdmann R (1999) Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2-dependent protein import into peroxisomes. J Cell Biol 144:1151–1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glover JR, Andrews DW, Rachubinski RA (1994) Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer. Proc Natl Acad Sci U S A 91:10541–10545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould SG, Keller GA, Subramani S (1987) Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol 105:2923–2931

    Article  CAS  PubMed  Google Scholar 

  • Gould SJ, Kalish JE, Morrell JC, Bjorkman J, Urquhart AJ, Crane DI (1996) Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTS1 receptor. J Cell Biol 135:85–95

    Article  CAS  PubMed  Google Scholar 

  • Grou CP, Carvalho AF, Pinto MP, Wiese S, Piechura H, Meyer HE, Warscheid B, Sa-Miranda C, Azevedo JE (2008) Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor. J Biol Chem 283:14190–14197

    Article  CAS  PubMed  Google Scholar 

  • Grou CP, Carvalho AF, Pinto MP, Huybrechts SJ, Sa-Miranda C, Fransen M, Azevedo JE (2009) Properties of the ubiquitin-pex5p thiol ester conjugate. J Biol Chem 284:10504–10513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grou CP, Francisco T, Rodrigues TA, Freitas MO, Pinto MP, Carvalho AF, Domingues P, Wood SA, Rodriguez-Borges JE, Sa-Miranda C, Fransen M, Azevedo JE (2012) Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate. J Biol Chem 287:12815–12827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grunau S, Schliebs W, Linnepe R, Neufeld C, Cizmowski C, Reinartz B, Meyer HE, Warscheid B, Girzalsky W, Erdmann R (2009) Peroxisomal targeting of PTS2 pre-import complexes in the yeast Saccharomyces cerevisiae. Traffic 10:451–460

    Article  CAS  PubMed  Google Scholar 

  • Hagen S, Drepper F, Fischer S, Fodor K, Passon D, Platta HW, Zenn M, Schliebs W, Girzalsky W, Wilmanns M, Warscheid B, Erdmann R (2015) Structural insights into cargo recognition by the yeast PTS1 receptor. J Biol Chem 290:26610–26626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hattula K, Hirschberg D, Kalkkinen N, Butcher SJ, Ora A (2014) Association between the intrinsically disordered protein PEX19 and PEX3. PLoS ONE 9:e103101

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hazra PP, Suriapranata I, Snyder WB, Subramani S (2002) Peroxisome remnants in pex3delta cells and the requirement of Pex3p for interactions between the peroxisomal docking and translocation subcomplexes. Traffic 3:560–574

    Article  CAS  PubMed  Google Scholar 

  • Helm M, Luck C, Prestele J, Hierl G, Huesgen PF, Frohlich T, Arnold GJ, Adamska I, Gorg A, Lottspeich F, Gietl C (2007) Dual specificities of the glyoxysomal/peroxisomal processing protease Deg15 in higher plants. Proc Natl Acad Sci U S A 104:11501–11506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hensel A, Beck S, El Magraoui F, Platta HW, Girzalsky W, Erdmann R (2011) Cysteine-dependent ubiquitination of Pex18p is linked to cargo translocation across the peroxisomal membrane. J Biol Chem 286:43495–43505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF (2005) Contribution of the endoplasmic reticulum to peroxisome formation. Cell 122:85–95

    Article  CAS  PubMed  Google Scholar 

  • Honsho M, Fujiki Y (2001) Topogenesis of peroxisomal membrane protein requires a short, positively charged intervening-loop sequence and flanking hydrophobic segments. Study using human membrane protein PMP34. J Biol Chem 276:9375–9382

    Article  PubMed  Google Scholar 

  • Hutchins AP, Liu S, Diez D, Miranda-Saavedra D (2013) The repertoires of ubiquitinating and deubiquitinating enzymes in eukaryotic genomes. Mol Biol Evol 30:1172–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islinger M, Li KW, Seitz J, Volkl A, Luers GH (2009) Hitchhiking of Cu/Zn superoxide dismutase to peroxisomes–evidence for a natural piggyback import mechanism in mammals. Traffic 10:1711–1721

    Article  CAS  PubMed  Google Scholar 

  • Jones JM, Morrell JC, Gould SJ (2001) Multiple distinct targeting signals in integral peroxisomal membrane proteins. J Cell Biol 153:1141–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones JM, Morrell JC, Gould SJ (2004) PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins. J Cell Biol 164:57–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung S, Marelli M, Rachubinski RA, Goodlett DR, Aitchison JD (2010) Dynamic changes in the subcellular distribution of Gpd1p in response to cell stress. J Biol Chem 285:6739–6749

    Article  CAS  PubMed  Google Scholar 

  • Kalel VC, Schliebs W, Erdmann R (2015) Identification and functional characterization of Trypanosoma brucei peroxin 16. Biochim Biophys Acta 1853:2326–2337

    Article  CAS  PubMed  Google Scholar 

  • Kaur N, Zhao Q, Xie Q, Hu J (2013) Arabidopsis RING peroxins are E3 ubiquitin ligases that interact with two homologous ubiquitin receptor proteins(F). J Integr Plant Biol 55:108–120

    Article  CAS  PubMed  Google Scholar 

  • Kiel JA, Emmrich K, Meyer HE, Kunau WH (2005) Ubiquitination of the peroxisomal targeting signal type 1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import. J Biol Chem 280:1921–1930

    Article  CAS  PubMed  Google Scholar 

  • Kiel JA, Veenhuis M, van der Klei IJ (2006) PEX genes in fungal genomes: common, rare or redundant. Traffic 7:1291–1303

    Article  CAS  PubMed  Google Scholar 

  • Knoops K, Manivannan S, Cepinska MN, Krikken AM, Kram AM, Veenhuis M, van der Klei IJ (2014) Preperoxisomal vesicles can form in the absence of Pex3. J Cell Biol 204:659–668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koller A, Snyder WB, Faber KN, Wenzel TJ, Rangell L, Keller GA, Subramani S (1999) Pex22p of Pichia pastoris, essential for peroxisomal matrix protein import, anchors the ubiquitin-conjugating enzyme, Pex4p, on the peroxisomal membrane. J Cell Biol 146:99–112

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kragt A, Voorn-Brouwer T, van den Berg M, Distel B (2005) The Saccharomyces cerevisiae peroxisomal import receptor Pex5p is monoubiquitinated in wild type cells. J Biol Chem 280:7867–7874

    Article  CAS  PubMed  Google Scholar 

  • Kurochkin IV, Mizuno Y, Konagaya A, Sakaki Y, Schonbach C, Okazaki Y (2007) Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in beta-oxidation of fatty acids. EMBO J 26:835–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lametschwandtner G, Brocard C, Fransen M, Van Veldhoven P, Berger J, Hartig A (1998) 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. J Biol Chem 273:33635–33643

    Article  CAS  PubMed  Google Scholar 

  • Léon S, Subramani S (2007) A conserved cysteine residue of Pichia pastoris Pex20p is essential for its recycling from the peroxisome to the cytosol. J Biol Chem 282:7424–7430

    Article  PubMed  CAS  Google Scholar 

  • Léon S, Zhang L, McDonald WH, Yates J 3rd, Cregg JM, Subramani S (2006) Dynamics of the peroxisomal import cycle of PpPex20p: ubiquitin-dependent localization and regulation. J Cell Biol 172:67–78

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Liu X, Subramani S (2013) Unique requirements for mono- and polyubiquitination of the peroxisomal targeting signal co-receptor, Pex20. J Biol Chem 288:7230–7240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F, Lu Y, Pieuchot L, Dhavale T, Jedd G (2011) Import oligomers induce positive feedback to promote peroxisome differentiation and control organelle abundance. Dev Cell 21:457–468

    Article  CAS  PubMed  Google Scholar 

  • Ma C, Schumann U, Rayapuram N, Subramani S (2009) The peroxisomal matrix import of Pex8p requires only PTS receptors and Pex14p. Mol Biol Cell 20:3680–3689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma C, Hagstrom D, Polley SG, Subramani S (2013) Redox-regulated cargo binding and release by the peroxisomal targeting signal receptor, Pex5. J Biol Chem 288:27220–27231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Managadze D, Wurtz C, Wiese S, Schneider M, Girzalsky W, Meyer HE, Erdmann R, Warscheid B, Rottensteiner H (2010) Identification of PEX33, a novel component of the peroxisomal docking complex in the filamentous fungus Neurospora crassa. Eur J Cell Biol 89:955–964

    Article  CAS  PubMed  Google Scholar 

  • Marzioch M, Erdmann R, Veenhuis M, Kunau WH (1994) PAS7 encodes a novel yeast member of the WD-40 protein family essential for import of 3-oxoacyl-CoA thiolase, a PTS2-containing protein, into peroxisomes. EMBO J 13:4908–4918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuzaki T, Fujiki Y (2008) The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p- and Pex16p-dependent pathway. J Cell Biol 183:1275–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meinecke M, Cizmowski C, Schliebs W, Kruger V, Beck S, Wagner R, Erdmann R (2010) The peroxisomal importomer constitutes a large and highly dynamic pore. Nat Cell Biol 12:273–277

    Article  CAS  PubMed  Google Scholar 

  • Montilla-Martinez M, Beck S, Klumper J, Meinecke M, Schliebs W, Wagner R, Erdmann R (2015) Distinct pores for peroxisomal import of PTS1 and PTS2 proteins. Cell Rep 13:2126–2134

    Article  CAS  PubMed  Google Scholar 

  • Neufeld C, Filipp FV, Simon B, Neuhaus A, Schuller N, David C, Kooshapur H, Madl T, Erdmann R, Schliebs W, Wilmanns M, Sattler M (2009) Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19. EMBO J 28:745–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oeljeklaus S, Reinartz BS, Wolf J, Wiese S, Tonillo J, Podwojski K, Kuhlmann K, Stephan C, Meyer HE, Schliebs W, Brocard C, Erdmann R, Warscheid B (2012) Identification of core components and transient interactors of the peroxisomal importomer by dual-track stable isotope labeling with amino acids in cell culture analysis. J Proteome Res 11:2567–2580

    Article  CAS  PubMed  Google Scholar 

  • Oeljeklaus S, Schummer A, Mastalski T, Platta HW, Warscheid B (2016) Regulation of peroxisome dynamics by phosphorylation. Biochim Biophys Acta 1863:1027–1037

    Article  CAS  PubMed  Google Scholar 

  • Okumoto K, Kametani Y, Fujiki Y (2011) Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid beta-oxidation in peroxisomal matrix. J Biol Chem 286:44367–44379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palma JM, Sandalio LM, Corpas FJ, Romero-Puertas MC, McCarthy I, del Río LA (2002) Plant proteases, protein degradation and oxidative stress: role of peroxisomes. Plant Physiol Biochem 40:521–530

    Article  CAS  Google Scholar 

  • Pan D, Nakatsu T, Kato H (2013) Crystal structure of peroxisomal targeting signal-2 bound to its receptor complex Pex7p-Pex21p. Nat Struct Mol Biol 20:987–993

    Article  CAS  PubMed  Google Scholar 

  • Petriv OI, Tang L, Titorenko VI, Rachubinski RA (2004) A new definition for the consensus sequence of the peroxisome targeting signal type 2. J Mol Biol 341:119–134

    Article  CAS  PubMed  Google Scholar 

  • Pires JR, Hong X, Brockmann C, Volkmer-Engert R, Schneider-Mergener J, Oschkinat H, Erdmann R (2003) The ScPex13p SH3 domain exposes two distinct binding sites for Pex5p and Pex14p. J Mol Biol 326:1427–1435

    Article  CAS  PubMed  Google Scholar 

  • Platta HW, Girzalsky W, Erdmann R (2004) Ubiquitination of the peroxisomal import receptor Pex5p. Biochem J 384:37–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Platta HW, Grunau S, Rosenkranz K, Girzalsky W, Erdmann R (2005) Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol 7:817–822

    Article  CAS  PubMed  Google Scholar 

  • Platta HW, El Magraoui F, Baumer BE, Schlee D, Girzalsky W, Erdmann R (2009) Pex2 and pex12 function as protein-ubiquitin ligases in peroxisomal protein import. Mol Cell Biol 29:5505–5516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Platta HW, Hagen S, Reidick C, Erdmann R (2014) The peroxisomal receptor dislocation pathway: to the exportomer and beyond. Biochimie 98:16–28

    Article  CAS  PubMed  Google Scholar 

  • Rehling P, Skaletz-Rorowski A, Girzalsky W, Voorn-Brouwer T, Franse MM, Distel B, Veenhuis M, Kunau WH, Erdmann R (2000) Pex8p, an intraperoxisomal peroxin of Saccharomyces cerevisiae required for protein transport into peroxisomes binds the PTS1 receptor pex5p. J Biol Chem 275:3593–3602

    Article  CAS  PubMed  Google Scholar 

  • Reumann S (2004) Specification of the peroxisome targeting signals type 1 and type 2 of plant peroxisomes by bioinformatics analyses. Plant Physiol 135:783–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reumann S, Babujee L, Ma C, Wienkoop S, Siemsen T, Antonicelli GE, Rasche N, Luder F, Weckwerth W, Jahn O (2007) Proteome analysis of Arabidopsis leaf peroxisomes reveals novel targeting peptides, metabolic pathways, and defense mechanisms. Plant Cell 19:3170–3193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rottensteiner H, Kramer A, Lorenzen S, Stein K, Landgraf C, Volkmer-Engert R, Erdmann R (2004) Peroxisomal membrane proteins contain common Pex19p-binding sites that are an integral part of their targeting signals. Mol Biol Cell 15:3406–3417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rucktäschel R, Thoms S, Sidorovitch V, Halbach A, Pechlivanis M, Volkmer R, Alexandrov K, Kuhlmann J, Rottensteiner H, Erdmann R (2009) Farnesylation of pex19p is required for its structural integrity and function in peroxisome biogenesis. J Biol Chem 284:20885–20896

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sato Y, Shibata H, Nakatsu T, Nakano H, Kashiwayama Y, Imanaka T, Kato H (2010) Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p. EMBO J 29:4083–4093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schäfer A, Kerssen D, Veenhuis M, Kunau WH, Schliebs W (2004) Functional similarity between the peroxisomal PTS2 receptor binding protein Pex18p and the N-terminal half of the PTS1 receptor Pex5p. Mol Cell Biol 24:8895–8906

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Schliebs W, Kunau WH (2006) PTS2 co-receptors: diverse proteins with common features. Biochim Biophys Acta 1763:1605–1612

    Article  CAS  PubMed  Google Scholar 

  • Schmidt O, Harbauer AB, Rao S, Eyrich B, Zahedi RP, Stojanovski D, Schonfisch B, Guiard B, Sickmann A, Pfanner N, Meisinger C (2011) Regulation of mitochondrial protein import by cytosolic kinases. Cell 144:227–239

    Article  CAS  PubMed  Google Scholar 

  • Schummer A, Fischer S, Oeljeklaus S, Warscheid B (2017) Study of peroxisomal protein phosphorylation by functional proteomics. Methods Mol Biol 1595:267–289

    Article  CAS  PubMed  Google Scholar 

  • Smith JJ, Sydorskyy Y, Marelli M, Hwang D, Bolouri H, Rachubinski RA, Aitchison JD (2006) Expression and functional profiling reveal distinct gene classes involved in fatty acid metabolism. Mol Syst Biol 2(2006):0009

    PubMed  Google Scholar 

  • Swinkels BW, Gould SJ, Bodnar AG, Rachubinski RA, Subramani S (1991) A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase. EMBO J 10:3255–3262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terlecky SR, Nuttley WM, McCollum D, Sock E, Subramani S (1995) The Pichia pastoris peroxisomal protein PAS8p is the receptor for the C-terminal tripeptide peroxisomal targeting signal. EMBO J 14:3627–3634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsukamoto T, Yokota S, Fujiki Y (1990) Isolation and characterization of Chinese hamster ovary cell mutants defective in assembly of peroxisomes. J Cell Biol 110:651–660

    Article  CAS  PubMed  Google Scholar 

  • Urquhart AJ, Kennedy D, Gould SJ, Crane DI (2000) Interaction of Pex5p, the type 1 peroxisome targeting signal receptor, with the peroxisomal membrane proteins Pex14p and Pex13p. J Biol Chem 275:4127–4136

    Article  CAS  PubMed  Google Scholar 

  • van der Klei IJ, Veenhuis M (2006) PTS1-independent sorting of peroxisomal matrix proteins by Pex5p. Biochim Biophys Acta 1763:1794–1800

    Article  PubMed  Google Scholar 

  • van der Klei IJ, Hilbrands RE, Kiel JA, Rasmussen SW, Cregg JM, Veenhuis M (1998) The ubiquitin-conjugating enzyme Pex4p of Hansenula polymorpha is required for efficient functioning of the PTS1 import machinery. EMBO J 17:3608–3618

    Article  PubMed  PubMed Central  Google Scholar 

  • Verplaetse E, Rigden DJ, Michels PA (2009) Identification, characterization and essentiality of the unusual peroxin 13 from Trypanosoma brucei. Biochim Biophys Acta 1793:516–527

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Visser NV, Veenhuis M, van der Klei IJ (2003) Physical interactions of the peroxisomal targeting signal 1 receptor pex5p, studied by fluorescence correlation spectroscopy. J Biol Chem 278:43340–43345

    Article  CAS  PubMed  Google Scholar 

  • Wiebel FF, Kunau WH (1992) The Pas2 protein essential for peroxisome biogenesis is related to ubiquitin-conjugating enzymes. Nature 359:73–76

    Article  CAS  PubMed  Google Scholar 

  • Williams C, van den Berg M, Geers E, Distel B (2008) Pex10p functions as an E3 ligase for the Ubc4p-dependent ubiquitination of Pex5p. Biochem Biophys Res Commun 374:620–624

    Article  CAS  PubMed  Google Scholar 

  • Williams C, van den Berg M, Panjikar S, Stanley WA, Distel B, Wilmanns M (2012) Insights into ubiquitin-conjugating enzyme/co-activator interactions from the structure of the Pex4p:Pex22p complex. EMBO J 31:391–402

    Article  CAS  PubMed  Google Scholar 

  • Wroblewska JP, Cruz-Zaragoza LD, Yuan W, Schummer A, Chuartzman SG, de Boer R, Oeljeklaus S, Schuldiner M, Zalckvar E, Warscheid B, Erdmann R, van der Klei IJ (2017) Saccharomyces cerevisiae cells lacking Pex3 contain membrane vesicles that harbor a subset of peroxisomal membrane proteins. Biochim Biophys Acta 1864:1656–1667

    Article  CAS  Google Scholar 

  • Yang X, Purdue PE, Lazarow PB (2001) Eci1p uses a PTS1 to enter peroxisomes: either its own or that of a partner, Dci1p. Eur J Cell Biol 80:126–138

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Leon S, Subramani S (2006) Two independent pathways traffic the intraperoxisomal peroxin PpPex8p into peroxisomes: mechanism and evolutionary implications. Mol Biol Cell 17:690–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work is supported by a FoRUM Grant (F883-2016, F913-2017) of the Ruhr-University Bochum and by the Deutsche Forschungsgemeinschaft (FOR1905). The authors apologize to all those in the community whose work could not be discussed due to space limitations.

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  1. Department of Systems Biochemistry, Faculty of Medicine, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Universitätsstr. 150, 44801, Bochum, Germany

    Vishal C. Kalel & Ralf Erdmann

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  1. Vishal C. Kalel
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  2. Ralf Erdmann
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Correspondence to Vishal C. Kalel .

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  1. Department of Biochemistry, Cell and Molecular Biology of Plants, Estación Experimental del Zaidín, CSIC, Granada, Spain

    Luis A. del Río

  2. Department of Biosciences, University of Exeter, Exeter, UK

    Michael Schrader

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Kalel, V.C., Erdmann, R. (2018). Unraveling of the Structure and Function of Peroxisomal Protein Import Machineries. In: del Río, L., Schrader, M. (eds) Proteomics of Peroxisomes. Subcellular Biochemistry, vol 89. Springer, Singapore. https://doi.org/10.1007/978-981-13-2233-4_13

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