Structure Biology of Peroxisomal Proteins, Peroxins

  • Hiroaki KatoEmail author


Peroxins participate in importing necessary proteins into the peroxisomes as well as producing the membrane that separates the peroxisome from the rest of the cell. One of the most powerful ways to elucidate the mechanisms underlying biological phenomena is to determine the three-dimensional structure of the macromolecules and their complexes. This review summarizes recent findings on available structural data of peroxins and their complexes. It provides structure-based mechanistic interpretation of the processes they are involved in, especially, two cases of structural investigations for PTS2 recognition complex that consists of Pex7p, Pex21p and an artificial PTS2-cargo protein, and for the complex of PMP carrier Pex19p and its receptor Pex3p. Recent breakthroughs in cryo-electron microscopy and X-ray free electron lasers have accelerated structural studies of difficult-to-crystallize proteins and have opened up new opportunities in understanding conformational dynamics and visualizing the process of biological actions. Their current results related to peroxins and future prospects are also explained to non-structural biologists.


Pex3 Pex7 Pex19 Pex21 PTS2 X-ray crystallography Intrinsically disordered proteins X-ray free electron laser (XFEL) Cryo-electron microscopy (Cryo-EM) AAA+ ATPase 


  1. Abe Y, Shodai T, Muto T, Mihara K, Torii H, Nishikawa S, Endo T, Kohda D (2000) Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100(5):551–560CrossRefGoogle Scholar
  2. Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S (2016) 2.3 A resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science 351(6275):871–875. Scholar
  3. Barros-Barbosa A, Rodrigues TA, Ferreira MJ, Pedrosa AG, Teixeira NR, Francisco T, Azevedo JE (2019) The intrinsically disordered nature of the peroxisomal protein translocation machinery. FEBS J 286(1):24–38. Scholar
  4. Blok NB, Tan D, Wang RY, Penczek PA, Baker D, DiMaio F, Rapoport TA, Walz T (2015) Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc Natl Acad Sci U S A 112(30):E4017–E4025. Scholar
  5. Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, Valle D (1997) Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet 15(4):369–376. Scholar
  6. Braverman N, Dodt G, Gould SJ, Valle D (1998) An isoform of pex5p, the human PTS1 receptor, is required for the import of PTS2 proteins into peroxisomes. Hum Mol Genet 7(8):1195–1205CrossRefGoogle Scholar
  7. Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, Chakraborty PK, Clarke JT, Boneh A, Moser A, Moser H, Valle D (2002) Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum Mutat 20(4):284–297. Scholar
  8. Chapman HN, Fromme P, Barty A, White TA, Kirian RA, Aquila A, Hunter MS, Schulz J, DePonte DP, Weierstall U, Doak RB, Maia FR, Martin AV, Schlichting I, Lomb L, Coppola N, Shoeman RL, Epp SW, Hartmann R, Rolles D, Rudenko A, Foucar L, Kimmel N, Weidenspointner G, Holl P, Liang M, Barthelmess M, Caleman C, Boutet S, Bogan MJ, Krzywinski J, Bostedt C, Bajt S, Gumprecht L, Rudek B, Erk B, Schmidt C, Homke A, Reich C, Pietschner D, Struder L, Hauser G, Gorke H, Ullrich J, Herrmann S, Schaller G, Schopper F, Soltau H, Kuhnel KU, Messerschmidt M, Bozek JD, Hau-Riege SP, Frank M, Hampton CY, Sierra RG, Starodub D, Williams GJ, Hajdu J, Timneanu N, Seibert MM, Andreasson J, Rocker A, Jonsson O, Svenda M, Stern S, Nass K, Andritschke R, Schroter CD, Krasniqi F, Bott M, Schmidt KE, Wang X, Grotjohann I, Holton JM, Barends TR, Neutze R, Marchesini S, Fromme R, Schorb S, Rupp D, Adolph M, Gorkhover T, Andersson I, Hirsemann H, Potdevin G, Graafsma H, Nilsson B, Spence JC (2011) Femtosecond X-ray protein nanocrystallography. Nature 470(7332):73–77. Scholar
  9. 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. Scholar
  10. Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Maser 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(6332):1416–1420. Scholar
  11. Dodt G, Warren D, Becker E, Rehling P, Gould SJ (2001) Domain mapping of human PEX5 reveals functional and structural similarities to Saccharomyces cerevisiae Pex18p and Pex21p. J Biol Chem 276(45):41769–41781. Scholar
  12. 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(5):1007–1017CrossRefGoogle Scholar
  13. Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197–208. nrm1589 [pii]CrossRefGoogle Scholar
  14. Einwachter H, Sowinski S, Kunau WH, Schliebs W (2001) Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway. EMBO Rep 2(11):1035–1039. Scholar
  15. 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. Scholar
  16. 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(6):863–875. jcb.200311131 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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(23):3743–3762. Scholar
  18. Fodor K, Wolf J, Erdmann R, Schliebs W, Wilmanns M (2012) Molecular requirements for peroxisomal targeting of alanine-glyoxylate aminotransferase as an essential determinant in primary hyperoxaluria type 1. PLoS Biol 10(4):e1001309. PBIOLOGY-D-11-04741 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  19. Fodor K, Wolf J, Reglinski K, Passon DM, Lou Y, Schliebs W, Erdmann R, Wilmanns M (2015) Ligand-induced compaction of the PEX5 receptor-binding cavity impacts protein import efficiency into peroxisomes. Traffic 16(1):85–98. Scholar
  20. Fransen M, Vastiau I, Brees C, Brys V, Mannaerts GP, Van Veldhoven PP (2005) Analysis of human Pex19p’s domain structure by pentapeptide scanning mutagenesis. J Mol Biol 346(5):1275–1286. S0022-2836(05)00035-5 [pii]CrossRefPubMedGoogle Scholar
  21. Fujiki Y, Matsuzono Y, Matsuzaki T, Fransen M (2006) Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions. Biochim Biophys Acta 1763(12):1639–1646. S0167-4889(06)00304-1 [pii]CrossRefPubMedGoogle Scholar
  22. Fujiki Y, Okumoto K, Mukai S, Honsho M, Tamura S (2014) Peroxisome biogenesis in mammalian cells. Front Physiol 5:307. Scholar
  23. Gardner BM, Chowdhury S, Lander GC, Martin A (2015) The Pex1/Pex6 complex is a heterohexameric AAA+ motor with alternating and highly coordinated subunits. J Mol Biol 427(6 Pt B):1375–1388. Scholar
  24. Gardner BM, Castanzo DT, Chowdhury S, Stjepanovic G, Stefely MS, Hurley JH, Lander GC, Martin A (2018) The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. Nat Commun 9(1):135. Scholar
  25. Gati C, Oberthuer D, Yefanov O, Bunker RD, Stellato F, Chiu E, Yeh SM, Aquila A, Basu S, Bean R, Beyerlein KR, Botha S, Boutet S, DePonte DP, Doak RB, Fromme R, Galli L, Grotjohann I, James DR, Kupitz C, Lomb L, Messerschmidt M, Nass K, Rendek K, Shoeman RL, Wang D, Weierstall U, White TA, Williams GJ, Zatsepin NA, Fromme P, Spence JC, Goldie KN, Jehle JA, Metcalf P, Barty A, Chapman HN (2017) Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser. Proc Natl Acad Sci U S A 114(9):2247–2252. Scholar
  26. Gatto GJ Jr, Geisbrecht BV, Gould SJ, Berg JM (2000) Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nat Struct Biol 7(12):1091–1095. Scholar
  27. Geuze HJ, Murk JL, Stroobants AK, Griffith JM, Kleijmeer MJ, Koster AJ, Verkleij AJ, Distel B, Tabak HF (2003) Involvement of the endoplasmic reticulum in peroxisome formation. Mol Biol Cell 14(7):2900–2907. E02-11-0734 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ghaedi K, Tamura S, Okumoto K, Matsuzono Y, Fujiki Y (2000) The peroxin pex3p initiates membrane assembly in peroxisome biogenesis. Mol Biol Cell 11(6):2085–2102CrossRefGoogle Scholar
  29. Glover JR, Andrews DW, Subramani S, Rachubinski RA (1994) Mutagenesis of the amino targeting signal of Saccharomyces cerevisiae 3-ketoacyl-CoA thiolase reveals conserved amino acids required for import into peroxisomes in vivo. J Biol Chem 269(10):7558–7563PubMedGoogle Scholar
  30. Groves MR, Schroer CFE, Middleton AJ, Lunev S, Danda N, Ali AM, Marrink SJ, Williams C (2018) Structural insights into K48-linked ubiquitin chain formation by the Pex4p-Pex22p complex. Biochem Biophys Res Commun 496(2):562–567. Scholar
  31. 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(50):43495–43505. Scholar
  32. Huang R, Ripstein ZA, Augustyniak R, Lazniewski M, Ginalski K, Kay LE, Rubinstein JL (2016) Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study. Proc Natl Acad Sci U S A 113(29):E4190–E4199. Scholar
  33. Janda CY, Li J, Oubridge C, Hernandez H, Robinson CV, Nagai K (2010) Recognition of a signal peptide by the signal recognition particle. Nature 465(7297):507–510. Scholar
  34. 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(1):57–67. jcb.200304111 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kammerer S, Holzinger A, Welsch U, Roscher AA (1998) Cloning and characterization of the gene encoding the human peroxisomal assembly protein Pex3p. FEBS Lett 429(1):53–60. S0014-5793(98)00557-2 [pii]CrossRefGoogle Scholar
  36. Khan BR, Zolman BK (2010) pex5 Mutants that differentially disrupt PTS1 and PTS2 peroxisomal matrix protein import in Arabidopsis. Plant Physiol 154(4):1602–1615. 110.162479 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  37. Kim PK, Mullen RT, Schumann U, Lippincott-Schwartz J (2006) The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER. J Cell Biol 173(4):521–532. jcb.200601036 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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(1):99–112. Scholar
  39. Kuhlbrandt W (2014) Biochemistry. The resolution revolution. Science 343(6178):1443–1444. Scholar
  40. Leon 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(10):7424–7430. Scholar
  41. Leon S, Zhang L, McDonald WH, Yates J III, Cregg JM, Subramani S (2006) Dynamics of the peroxisomal import cycle of PpPex20p: ubiquitin-dependent localization and regulation. J Cell Biol 172(1):67–78. Scholar
  42. Li X, Mooney P, Zheng S, Booth CR, Braunfeld MB, Gubbens S, Agard DA, Cheng Y (2013) Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat Methods 10(6):584–590. Scholar
  43. Liu W, Wacker D, Gati C, Han GW, James D, Wang D, Nelson G, Weierstall U, Katritch V, Barty A, Zatsepin NA, Li D, Messerschmidt M, Boutet S, Williams GJ, Koglin JE, Seibert MM, Wang C, Shah ST, Basu S, Fromme R, Kupitz C, Rendek KN, Grotjohann I, Fromme P, Kirian RA, Beyerlein KR, White TA, Chapman HN, Caffrey M, Spence JC, Stevens RC, Cherezov V (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science 342(6165):1521–1524. Scholar
  44. 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(20):4908–4918CrossRefGoogle Scholar
  45. Matsumura T, Otera H, Fujiki Y (2000) Disruption of the interaction of the longer isoform of Pex5p, Pex5pL, with Pex7p abolishes peroxisome targeting signal type 2 protein import in mammals. Study with a novel Pex5-impaired Chinese hamster ovary cell mutant. J Biol Chem 275(28):21715–21721. M000721200 [pii]CrossRefPubMedGoogle Scholar
  46. Matsuzono Y, Kinoshita N, Tamura S, Shimozawa N, Hamasaki M, Ghaedi K, Wanders RJ, Suzuki Y, Kondo N, Fujiki Y (1999) Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc Natl Acad Sci U S A 96(5):2116–2121CrossRefGoogle Scholar
  47. Matsuzono Y, Matsuzaki T, Fujiki Y (2006) Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential for function and translocation. J Cell Sci 119(Pt 17):3539–3550. jcs.03100 [pii]CrossRefPubMedGoogle Scholar
  48. Mizohata E, Nakane T, Fukuda Y, Nango E, Iwata S (2018) Serial femtosecond crystallography at the SACLA: breakthrough to dynamic structural biology. Biophys Rev 10(2):209–218. Scholar
  49. Motley AM, Hettema EH, Hogenhout EM, Brites P, ten Asbroek AL, Wijburg FA, Baas F, Heijmans HS, Tabak HF, Wanders RJ, Distel B (1997) Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor. Nat Genet 15(4):377–380. Scholar
  50. Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJ, Waterham HR (2002) Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. Am J Hum Genet 70(3):612–624. S0002-9297(07)60265-1 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  51. Muntau AC, Mayerhofer PU, Paton BC, Kammerer S, Roscher AA (2000) Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am J Hum Genet 67(4):967–975. S0002-9297(07)63288-1 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  52. 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(6):745–754. emboj20097 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  53. Neuhaus A, Kooshapur H, Wolf J, Meyer NH, Madl T, Saidowsky J, Hambruch E, Lazam A, Jung M, Sattler M, Schliebs W, Erdmann R (2014) A novel Pex14 protein-interacting site of human Pex5 is critical for matrix protein import into peroxisomes. J Biol Chem 289(1):437–448. Scholar
  54. Neutze R, Wouts R, van der Spoel D, Weckert E, Hajdu J (2000) Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406(6797):752–757. Scholar
  55. Nito K, Hayashi M, Nishimura M (2002) Direct interaction and determination of binding domains among peroxisomal import factors in Arabidopsis thaliana. Plant Cell Physiol 43(4):355–366CrossRefGoogle Scholar
  56. Osumi T, Tsukamoto T, Hata S, Yokota S, Miura S, Fujiki Y, Hijikata M, Miyazawa S, Hashimoto T (1991) Amino-terminal presequence of the precursor of peroxisomal 3-ketoacyl-CoA thiolase is a cleavable signal peptide for peroxisomal targeting. Biochem Biophys Res Commun 181(3):947–954CrossRefGoogle Scholar
  57. Otera H, Okumoto K, Tateishi K, Ikoma Y, Matsuda E, Nishimura M, Tsukamoto T, Osumi T, Ohashi K, Higuchi O, Fujiki Y (1998) Peroxisome targeting signal type 1 (PTS1) receptor is involved in import of both PTS1 and PTS2: studies with PEX5-defective CHO cell mutants. Mol Cell Biol 18(1):388–399CrossRefGoogle Scholar
  58. Pan D, Nakatsu T, Kato H (2013) Crystal structure of peroxisomal terget signal-2 bound to its receptor complex Pex7p–Pex21p. Nat Struct Mol Biol 20(8):987–993. nsmb.2618 [pii]CrossRefPubMedGoogle Scholar
  59. 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(1):119–134. Scholar
  60. Pinto MP, Grou CP, Fransen M, Sa-Miranda C, Azevedo JE (2009) The cytosolic domain of PEX3, a protein involved in the biogenesis of peroxisomes, binds membrane lipids. Biochim Biophys Acta 1793(11):1669–1675. S0167-4889(09)00211-0 [pii]CrossRefPubMedGoogle Scholar
  61. 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(5):1427–1435CrossRefGoogle Scholar
  62. Platta HW, Erdmann R (2007) Peroxisomal dynamics. Trends Cell Biol 17(10):474–484. Scholar
  63. Purdue PE, Zhang JW, Skoneczny M, Lazarow PB (1997) Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. Nat Genet 15(4):381–384. Scholar
  64. Purdue PE, Yang X, Lazarow PB (1998) Pex18p and Pex21p, a novel pair of related peroxins essential for peroxisomal targeting by the PTS2 pathway. J Cell Biol 143(7):1859–1869CrossRefGoogle Scholar
  65. Rehling P, Marzioch M, Niesen F, Wittke E, Veenhuis M, Kunau WH (1996) The import receptor for the peroxisomal targeting signal 2 (PTS2) in Saccharomyces cerevisiae is encoded by the PAS7 gene. EMBO J 15(12):2901–2913CrossRefGoogle Scholar
  66. Ripstein ZA, Huang R, Augustyniak R, Kay LE, Rubinstein JL (2017) Structure of a AAA+ unfoldase in the process of unfolding substrate. eLife 6.
  67. Saffert P, Enenkel C, Wendler P (2017) Structure and function of p97 and Pex1/6 type II AAA+ complexes. Front Mol Biosci 4:33. Scholar
  68. Saitoh T, Igura M, Obita T, Ose T, Kojima R, Maenaka K, Endo T, Kohda D (2007) Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states. EMBO J 26(22):4777–4787. 7601888 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  69. Sampathkumar P, Roach C, Michels PA, Hol WG (2008) Structural insights into the recognition of peroxisomal targeting signal 1 by Trypanosoma brucei peroxin 5. J Mol Biol 381(4):867–880. S0022-2836(08)00760-2 [pii]CrossRefPubMedGoogle Scholar
  70. Sato Y, Shibata H, Nakano H, Matsuzono Y, Kashiwayama Y, Kobayashi Y, Fujiki Y, Imanaka T, Kato H (2008) Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p: identification of TRP-104 IN Pex3p as a critical residue for the interaction. J Biol Chem 283(10):6136–6144. Scholar
  71. 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(24):4083–4093. Scholar
  72. Schliebs W, Kunau WH (2006) PTS2 co-receptors: diverse proteins with common features. Biochim Biophys Acta 1763(12):1605–1612. Scholar
  73. Schmidt F, Treiber N, Zocher G, Bjelic S, Steinmetz MO, Kalbacher H, Stehle T, Dodt G (2010) Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19. J Biol Chem 285(33):25410–25417. M110.138503 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  74. Schueller N, Holton SJ, Fodor K, Milewski M, Konarev P, Stanley WA, Wolf J, Erdmann R, Schliebs W, Song YH, Wilmanns M (2010) The peroxisomal receptor Pex19p forms a helical mPTS recognition domain. EMBO J 29(15):2491–2500. emboj2010115 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  75. Schuller JM, Beck F, Lossl P, Heck AJ, Forster F (2016) Nucleotide-dependent conformational changes of the AAA+ ATPase p97 revisited. FEBS Lett 590(5):595–604. Scholar
  76. Seibert MM, Ekeberg T, Maia FR, Svenda M, Andreasson J, Jonsson O, Odic D, Iwan B, Rocker A, Westphal D, Hantke M, DePonte DP, Barty A, Schulz J, Gumprecht L, Coppola N, Aquila A, Liang M, White TA, Martin A, Caleman C, Stern S, Abergel C, Seltzer V, Claverie JM, Bostedt C, Bozek JD, Boutet S, Miahnahri AA, Messerschmidt M, Krzywinski J, Williams G, Hodgson KO, Bogan MJ, Hampton CY, Sierra RG, Starodub D, Andersson I, Bajt S, Barthelmess M, Spence JC, Fromme P, Weierstall U, Kirian R, Hunter M, Doak RB, Marchesini S, Hau-Riege SP, Frank M, Shoeman RL, Lomb L, Epp SW, Hartmann R, Rolles D, Rudenko A, Schmidt C, Foucar L, Kimmel N, Holl P, Rudek B, Erk B, Homke A, Reich C, Pietschner D, Weidenspointner G, Struder L, Hauser G, Gorke H, Ullrich J, Schlichting I, Herrmann S, Schaller G, Schopper F, Soltau H, Kuhnel KU, Andritschke R, Schroter CD, Krasniqi F, Bott M, Schorb S, Rupp D, Adolph M, Gorkhover T, Hirsemann H, Potdevin G, Graafsma H, Nilsson B, Chapman HN, Hajdu J (2011) Single mimivirus particles intercepted and imaged with an X-ray laser. Nature 470(7332):78–81. Scholar
  77. Shibata H, Kashiwayama Y, Imanaka T, Kato H (2004) Domain architecture and activity of human Pex19p, a chaperone-like protein for intracellular trafficking of peroxisomal membrane proteins. J Biol Chem 279(37):38486–38494. M402204200 [pii]CrossRefPubMedGoogle Scholar
  78. Shimozawa N, Suzuki Y, Zhang Z, Imamura A, Ghaedi K, Fujiki Y, Kondo N (2000) Identification of PEX3 as the gene mutated in a Zellweger syndrome patient lacking peroxisomal remnant structures. Hum Mol Genet 9(13):1995–1999CrossRefGoogle Scholar
  79. Shiozawa K, Maita N, Tomii K, Seto A, Goda N, Akiyama Y, Shimizu T, Shirakawa M, Hiroaki H (2004) Structure of the N-terminal domain of PEX1 AAA-ATPase. Characterization of a putative adaptor-binding domain. J Biol Chem 279(48):50060–50068. Scholar
  80. Sichting M, Schell-Steven A, Prokisch H, Erdmann R, Rottensteiner H (2003) Pex7p and Pex20p of Neurospora crassa function together in PTS2-dependent protein import into peroxisomes. Mol Biol Cell 14(2):810–821. Scholar
  81. Smith JJ, Aitchison JD (2013) Peroxisomes take shape. Nat Rev Mol Cell Biol 14(12):803–817. Scholar
  82. Smith TF, Gaitatzes C, Saxena K, Neer EJ (1999) The WD repeat: a common architecture for diverse functions. Trends Biochem Sci 24(5):181–185CrossRefGoogle Scholar
  83. Soukupova M, Sprenger C, Gorgas K, Kunau WH, Dodt G (1999) Identification and characterization of the human peroxin PEX3. Eur J Cell Biol 78(6):357–374CrossRefGoogle Scholar
  84. Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M (2006) Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p. Mol Cell 24(5):653–663. S1097-2765(06)00730-1 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  85. Stanley WA, Pursiainen NV, Garman EF, Juffer AH, Wilmanns M, Kursula P (2007) A previously unobserved conformation for the human Pex5p receptor suggests roles for intrinsic flexibility and rigid domain motions in ligand binding. BMC Struct Biol 7:24. 1472-6807-7-24 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  86. Su JR, Takeda K, Tamura S, Fujiki Y, Miki K (2009) Crystal structure of the conserved N-terminal domain of the peroxisomal matrix protein import receptor, Pex14p. Proc Natl Acad Sci U S A 106(2):417–421. 0808681106 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  87. 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(11):3255–3262CrossRefGoogle Scholar
  88. van der Zand A, Braakman I, Tabak HF (2010) Peroxisomal membrane proteins insert into the endoplasmic reticulum. Mol Biol Cell 21(12):2057–2065. E10-02-0082 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  89. Vonck J, Parcej DN, Mills DJ (2016) Structure of alcohol oxidase from Pichia pastoris by cryo-electron microscopy. PLoS One 11(7):e0159476. Scholar
  90. Wanders RJ, Waterham HR (2006) Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem 75:295–332. Scholar
  91. Watanabe Y, Kawaguchi K, Okuyama N, Sugawara Y, Obita T, Mizuguchi M, Morita M, Imanaka T (2016) Characterization of the interaction between Trypanosoma brucei Pex5p and its receptor Pex14p. FEBS Lett 590(2):242–250. Scholar
  92. Wiedemann N, van der Laan M, Pfanner N (2009) SnapShot: import and sorting of mitochondrial proteins. Cell 138(4):808–808.e801. S0092-8674(09)00966-0 [pii]CrossRefPubMedGoogle Scholar
  93. 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(2):391–402. emboj2011411 [pii]CrossRefPubMedGoogle Scholar
  94. Williams C, van den Berg M, Stanley WA, Wilmanns M, Distel B (2013) A disulphide bond in the E2 enzyme Pex4p modulates ubiquitin-conjugating activity. Sci Rep 3:2212. srep02212 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  95. Yamashita K, Pan D, Okuda T, Sugahara M, Kodan A, Yamaguchi T, Murai T, Gomi K, Kajiyama N, Mizohata E, Suzuki M, Nango E, Tono K, Joti Y, Kameshima T, Park J, Song C, Hatsui T, Yabashi M, Iwata S, Kato H, Ago H, Yamamoto M, Nakatsu T (2015) An isomorphous replacement method for efficient de novo phasing for serial femtosecond crystallography. Sci Rep 5:14017. Scholar
  96. Yamashita K, Kuwabara N, Nakane T, Murai T, Mizohata E, Sugahara M, Pan D, Masuda T, Suzuki M, Sato T, Kodan A, Yamaguchi T, Nango E, Tanaka T, Tono K, Joti Y, Kameshima T, Hatsui T, Yabashi M, Manya H, Endo T, Kato R, Senda T, Kato H, Iwata S, Ago H, Yamamoto M, Yumoto F, Nakatsu T (2017) Experimental phase determination with selenomethionine or mercury-derivatization in serial femtosecond crystallography. IUCrJ 4(Pt 5):639–647. Scholar
  97. Yofe I, Soliman K, Chuartzman SG, Morgan B, Weill U, Yifrach E, Dick TP, Cooper SJ, Ejsing CS, Schuldiner M, Zalckvar E, Thoms S (2017) Pex35 is a regulator of peroxisome abundance. J Cell Sci 130(4):791–804. Scholar
  98. Young JC, Hoogenraad NJ, Hartl FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112(1):41–50. S0092867402012503 [pii]CrossRefGoogle Scholar
  99. Zhang JW, Lazarow PB (1995) PEB1 (PAS7) in Saccharomyces cerevisiae encodes a hydrophilic, intra-peroxisomal protein that is a member of the WD repeat family and is essential for the import of thiolase into peroxisomes. J Cell Biol 129(1):65–80CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Structural Biology, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan

Personalised recommendations