Pups, SAMPs, and Prokaryotic Proteasomes

Chapter
First Online:

Abstract

In eukaryotes, barrel-shaped proteases known as 26S proteasomes are responsible for removing misfolded proteins and regulatory proteins after they serve their function. 26S proteasomes are ATP-dependent proteases with three different proteolytic activities. The proteolytic active sites are segregated into the inner compartment of proteasome to prevent nonspecific degradation of cytosolic proteins. Eukaryotic cells tag the proteins with ubiquitin, in order to selectively target them for degradation by proteasomes. The presence of proteasomes in some species of actinobacteria and archaea is known for more than two decades. However, the details of the molecules used as tags and the mechanism of tagging are coming to light only in the recent times. In actinobacteria prokaryotic ubiquitin-like molecules (Pups) and in archaea small archaeal modifier proteins (SAMPs) are used as tags. Though prokaryotic proteasomes show homology to their eukaryotic counterparts, the prokaryotic tagging mechanism is vastly different suggesting convergent evolution. The structure of prokaryotic proteasomes, Pups, and SAMPs and the tagging mechanisms are presented here in detail, and the similarities and differences with eukaryotic system are highlighted. The possible applications of the knowledge generated in this area to the treatment of tuberculosis are underscored at the end of the chapter.

Keywords

Prokaryotic ubiquitin-like protein Pup Small archaeal modifier proteins SAMP1 SAMP2 Prokaryotic proteasomes 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    de Duve C, Pressman BC, Gianetto R, Wattiaux R, Appelmans F (1955) Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J 60:604–617CrossRefPubMedCentralGoogle Scholar
  2. 2.
    de Duve C (2005) The lysosome turns fifty. Nat Cell Biol 7:847–849CrossRefPubMedGoogle Scholar
  3. 3.
    Schultz ML, Tecedor L, Chang M, Davidson BL (2011) Clarifying lysosomal storage diseases. Trends Neurosci 34:401–410CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lieberman AP, Puertollano R, Raben N, Slaugenhaupt S, Walkley SU, Ballabio A (2012) Autophagy in lysosomal storage disorders. Autophagy 8:719–730CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Parenti G, Pignata C, Vajro P, Salerno M (2013) New strategies for the treatment of lysosomal storage diseases. Int J Mol Med 31:11–20PubMedGoogle Scholar
  6. 6.
    Xie Y (2010) Structure, assembly and homeostatic regulation of the 26S proteasome. J Mol Cell Biol 2:308–317CrossRefPubMedGoogle Scholar
  7. 7.
    Varshavsky A (2012) The ubiquitin system, an immense realm. Annu Rev Biochem 81:167–176CrossRefPubMedGoogle Scholar
  8. 8.
    Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479CrossRefPubMedGoogle Scholar
  9. 9.
    Glickman MH (2000) Getting in and out of the proteasome. Semin Cell Dev Biol 11:149–158CrossRefPubMedGoogle Scholar
  10. 10.
    Ciechanover A, Hod Y, Hershko A (2012) A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. 1978. Biochem Biophys Res Commun 425:565–570CrossRefPubMedGoogle Scholar
  11. 11.
    Goldstein G, Scheid M, Hammerling U, Schlesinger DH, Niall HD, Boyse EA (1975) Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Nat Acad Sci U S A 72:11–15CrossRefGoogle Scholar
  12. 12.
    Wilkinson KD (2005) The discovery of ubiquitin-dependent proteolysis. Proc Nat Acad Sci U S A 102:15280–15282CrossRefGoogle Scholar
  13. 13.
    Ciechanover A (2005) Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture). Angew Chem Int Ed Engl 44:5944–5967CrossRefPubMedGoogle Scholar
  14. 14.
    De Mot R, Nagy I, Walz J, Baumeister W (1999) Proteasomes and other self-compartmentalizing proteases in prokaryotes. Trends Microbiol 7:88–92CrossRefPubMedGoogle Scholar
  15. 15.
    Kwon YD, Nagy I, Adams PD, Baumeister W, Jap BK (2004) Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly. J Mol Biol 335:233–245CrossRefPubMedGoogle Scholar
  16. 16.
    Lin G, Hu G, Tsu C, Kunes YZ, Li H, Dick L, Parsons T, Li P, Chen Z, Zwickl P, Weich N, Nathan C (2006) Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity. Mol Microbiol 59:1405–1416CrossRefPubMedGoogle Scholar
  17. 17.
    Pouch M-N, Cournoyer B, Baumeister W (2000) Characterization of the 20S proteasome from the actinomycete Frankia. Mol Microbiol 35:368–377CrossRefPubMedGoogle Scholar
  18. 18.
    Tamura T, Nagy I, Lupas A, Lottspeich F, Cejka Z, Schoofs G, Tanaka K, De Mot R, Baumeister W (1995) The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus. Curr Biol 5:766–774CrossRefPubMedGoogle Scholar
  19. 19.
    Nagy I, Tamura T, Vanderleyden J, Baumeister W, De Mot R (1998) The 20S proteasome of Streptomyces coelicolor. J Bacteriol 180:5448–5453PubMedPubMedCentralGoogle Scholar
  20. 20.
    Akopian TN, Kisselev AF, Goldberg AL (1997) Processive degradation of proteins and other catalytic properties of the proteasome from Thermoplasma acidophilum. J Biol Chem 272:1791–1798CrossRefPubMedGoogle Scholar
  21. 21.
    Kaczowka SJ, Maupin-Furlow JA (2003) Subunit topology of two 20S proteasomes from Haloferax volcanii. J Bacteriol 185:165–174CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Humbard MA, Zhou G, Maupin-Furlow JA (2009) The N-terminal penultimate residue of 20S proteasome alpha1 influences its N(alpha) acetylation and protein levels as well as growth rate and stress responses of Haloferax volcanii. J Bacteriol 191:3794–3803CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Benaroudj N, Goldberg AL (2000) PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone. Nat Cell Biol 2:833–839CrossRefPubMedGoogle Scholar
  24. 24.
    Reuter CJ, Kaczowka SJ, Maupin-Furlow JA (2004) Differential regulation of the PanA and PanB proteasome-activating nucleotidase and 20S proteasomal proteins of the haloarchaeon Haloferax volcanii. J Bacteriol 186:7763–7772CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Benaroudj N, Zwickl P, Seemuller E, Baumeister W, Goldberg AL (2003) ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation. Mol Cell 11:69–78CrossRefPubMedGoogle Scholar
  26. 26.
    Smith DM, Kafri G, Cheng Y, Ng D, Walz T, Goldberg AL (2005) ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. Mol Cell 20:687–698CrossRefPubMedGoogle Scholar
  27. 27.
    Darwin KH, Lin G, Chen Z, Li H, Nathan C (2005) Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol Microbiol 55:561–571CrossRefPubMedGoogle Scholar
  28. 28.
    Wolf S, Nagy I, Lupas A, Pfeifer G, Cejka Z, Muller SA, Engel A, De Mot R, Baumeister W (1998) Characterization of ARC, a divergent member of the AAA ATPase family from Rhodococcus erythropolis. J Mol Biol 277:13–25CrossRefPubMedGoogle Scholar
  29. 29.
    Djuranovic S, Hartmann MD, Habeck M, Ursinus A, Zwickl P, Martin J, Lupas AN, Zeth K (2009) Structure and activity of the N-terminal substrate recognition domains in proteasomal ATPases. Mol Cell 34:580–590CrossRefPubMedGoogle Scholar
  30. 30.
    Rabl J, Smith DM, Yu Y, Chang SC, Goldberg AL, Cheng Y (2008) Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases. Mol Cell 30:360–368CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Smith DM, Chang SC, Park S, Finley D, Cheng Y, Goldberg AL (2007) Docking of the proteasomal ATPases’ carboxyl termini in the 20S proteasome’s alpha ring opens the gate for substrate entry. Mol Cell 27:731–744CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Wang T, Li H, Lin G, Tang C, Li D, Nathan C, Darwin KH (2009) Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa. Structure 17:1377–1385CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Striebel F, Hunkeler M, Summer H, Weber-Ban E (2010) The mycobacterial Mpa–proteasome unfolds and degrades pupylated substrates by engaging Pup’s N-terminus. EMBO J 29:1262–1271CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Burns KE, Liu WT, Boshoff HI, Dorrestein PC, Barry CE III (2009) Proteasomal protein degradation in mycobacteria is dependent upon a prokaryotic ubiquitin-like protein. J Biol Chem 284:3069–3075CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Pearce MJ, Mintseris J, Ferreyra J, Gygi SP, Darwin KH (2008) Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 322:1104–1107CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Striebel F, Imkamp F, Özcelik D, Weber-Ban E (2014) Pupylation as a signal for proteasomal degradation in bacteria. Biochim Biophys Acta 1843:103–113CrossRefPubMedGoogle Scholar
  37. 37.
    Sutter M, Striebel F, Damberger FF, Allain FH, Weber-Ban E (2009) A distinct structural region of the prokaryotic ubiquitin-like protein (pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett 583:3151–3157CrossRefPubMedGoogle Scholar
  38. 38.
    Chen X, Solomon WC, Kang Y, Cerda-Maira F, Darwin KH, Walters KJ (2009) Prokaryotic ubiquitin-like protein pup is intrinsically disordered. J Mol Biol 392:208–217CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Liao S, Shang Q, Zhang X, Zhang J, Xu C, Tu X (2009) Pup, a prokaryotic ubiquitin like protein, is an intrinsically disordered protein. Biochem J 422:207–215CrossRefPubMedGoogle Scholar
  40. 40.
    Striebel F, Imkamp F, Sutter M, Steiner M, Mamedov A, Weber-Ban E (2009) Bacterial ubiquitin-like modifier pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nat Struct Mol Biol 16:647–651CrossRefPubMedGoogle Scholar
  41. 41.
    Imkamp F, Rosenberger T, Striebel F, Keller PM, Amstutz B, Sander P, Weber-Ban E (2010) Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo. Mol Microbiol 75:744–754CrossRefPubMedGoogle Scholar
  42. 42.
    Cerda-Maira FA, Pearce MJ, Fuortes M, Bishai WR, Hubbard SR, Darwin KH (2010) Molecular analysis of the prokaryotic ubiquitin-like protein (pup) conjugation pathway in Mycobacterium tuberculosis. Mol Microbiol 77:1123–1135CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Pearce MJ, Arora P, Festa RA, Butler-Wu SM, Gokhale RS, Darwin KH (2006) Identification of substrates of the Mycobacterium tuberculosis proteasome. EMBO J 25: 5423–5432Google Scholar
  44. 44.
    Guth E, Thommen M, Weber-Ban E (2011) Mycobacterial ubiquitin-like protein ligase PafA follows a two-step reaction pathway with a phosphorylated pup intermediate. J Biol Chem 286:4412–4419CrossRefPubMedGoogle Scholar
  45. 45.
    Burns KE, Cerda-Maira FA, Wang T, Li H, Bishai WR, Darwin KH (2010) “Depupylation” of prokaryotic ubiquitin-like protein from mycobacterial proteasome substrates. Mol Cell 39:821–827CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Imkamp F, Striebel F, Sutter M, Özcelik D, Zimmermann N, Sander P, Weber-Ban E (2010) Dop functions as a depupylase in the prokaryotic ubiquitin-like modification pathway. EMBO Rep 11:791–797CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Wang T, Darwin KH, Li H (2010) Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation. Nat Struct Mol Biol 17:1352–1357CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Burns KE, Pearce MJ, Darwin KH (2010) Prokaryotic ubiquitin-like protein provides a two-part degron to Mycobacterium proteasome substrates. J Bacteriol 192:2933–2935CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Festa RA, McAllister F, Pearce MJ, Mintseris J, Burns KE, Gygi SP, Darwin KH (2010) Prokaryotic ubiquitin-like protein (pup) proteome of Mycobacterium tuberculosis [corrected]. PLoS One 5:e8589CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Watrous J, Burns K, Liu WT, Patel A, Hook V, Bafna V, Barry CE III, Bark S, Dorrestein PC (2010) Expansion of the mycobacterial “PUPylome”. Mol BioSyst 6:376–385CrossRefPubMedGoogle Scholar
  51. 51.
    Poulsen C, Akhter Y, Jeon AH, Schmitt-Ulms G, Meyer HE, Stefanski A, Stuhler K, Wilmanns M, Song YH (2010) Proteome-wide identification of mycobacterial pupylation targets. Mol Syst Biol 6:386CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Delley CL, Striebel F, Heydenreich FM, Ozcelik D, Weber-Ban E (2012) Activity of the mycobacterial proteasomal ATPase Mpa is reversibly regulated by pupylation. J Biol Chem 287:7907–7914CrossRefPubMedGoogle Scholar
  53. 53.
    Hong B, Wang L, Lammertyn E, Geukens N, Van Mellaert L, Li Y, Anne J (2005) Inactivation of the 20S proteasome in Streptomyces lividans and its influence on the production of heterologous proteins. Microbiology 151:3137–3145CrossRefPubMedGoogle Scholar
  54. 54.
    Knipfer N, Shrader TE (1997) Inactivation of the 20S proteasome in Mycobacterium smegmatis. Mol Microbiol 25:375–383CrossRefPubMedGoogle Scholar
  55. 55.
    Gandotra S, Lebron MB, Ehrt S (2010) The Mycobacterium tuberculosis proteasome active site threonine is essential for persistence yet dispensable for replication and resistance to nitric oxide. PLoS Pathog 6Google Scholar
  56. 56.
    Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S (2007) In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med 13:1515–1520CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Darwin KH, Ehrt S, Gutierrez-Ramos JC, Weich N, Nathan CF (2003) The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302:1963–1966CrossRefPubMedGoogle Scholar
  58. 58.
    Blumenthal A, Trujillo C, Ehrt S, Schnappinger D (2010) Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo. PLoS One 5:e15667CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Sassetti CM, Rubin EJ (2003) Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100:12989–12994CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Cerda-Maira F, Darwin KH (2009) The Mycobacterium tuberculosis proteasome: more than just a barrel-shaped protease. Microbes Infect 11:1150–1155CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    MacMicking JD, North RJ, LaCourse R, Mudgett JS, Shah SK, Nathan CF (1997) Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci U S A 94:5243–5248CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    McKinney JD, Honer zu Bentrup K, Munoz-Elias EJ, Miczak A, Chen B, Chan WT, Swenson D, Sacchettini JC, Jacobs Jr. WR, Russell DG (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406: 735–738Google Scholar
  63. 63.
    Movahedzadeh F, Smith DA, Norman RA, Dinadayala P, Murray-Rust J, Russell DG, Kendall SL, Rison SC, McAlister MS, Bancroft GJ, McDonald NQ, Daffe M, Av-Gay Y, Stoker NG (2004) The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence. Mol Microbiol 51:1003–1014CrossRefPubMedGoogle Scholar
  64. 64.
    Lin G, Tsu C, Dick L, Zhou XK, Nathan C (2008) Distinct specificities of Mycobacterium tuberculosis and mammalian proteasomes for N-acetyl tripeptide substrates. J Biol Chem 283: 34423–34431Google Scholar
  65. 65.
    Kropff MH, Bisping G, Wenning D, Volpert S, Tchinda J, Berdel WE, Kienast J (2005) Bortezomib in combination with dexamethasone for relapsed multiple myeloma. Leuk Res 29:587–590CrossRefPubMedGoogle Scholar
  66. 66.
    Lin G, Li D, de Carvalho LP, Deng H, Tao H, Vogt G, Wu K, Schneider J, Chidawanyika T, Warren JD, Li H, Nathan C (2009) Inhibitors selective for mycobacterial versus human proteasomes. Nature 461:621–626CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Valas RE, Bourne PE (2011) The origin of a derived superkingdom: how a gram-positive bacterium crossed the desert to become an archaeon. Biol Direct 6:16CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Volker C, Lupas AN (2002) Molecular evolution of proteasomes. Curr Top Microbiol Immunol 268:1–22PubMedGoogle Scholar
  69. 69.
    Gille C, Goede A, Schloetelburg C, Preissner R, Kloetzel PM, Gobel UB, Frommel C (2003) A comprehensive view on proteasomal sequences: implications for the evolution of the proteasome. J Mol Biol 326:1437–1448CrossRefPubMedGoogle Scholar
  70. 70.
    Eisenberg D, Gill HS, Pfluegl GM, Rotstein SH (2000) Structure–function relationships of glutamine synthetases. Biochim Biophys Acta 1477:122–145CrossRefPubMedGoogle Scholar
  71. 71.
    Gill HS, Eisenberg D (2001) The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition. Biochemistry 40:1903–1912CrossRefPubMedGoogle Scholar
  72. 72.
    Iyer LM, Burroughs AM, Aravind L (2006) The prokaryotic antecedents of the ubiquitin signaling system and the early evolution of ubiquitin-like beta-grasp domains. Genome Biol 7:R60CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Kessler D (2006) Enzymatic activation of sulfur for incorporation into biomolecules in prokaryotes. FEMS Microbiol Rev 30:825–840CrossRefPubMedGoogle Scholar
  74. 74.
    Leidel S, Pedrioli PG, Bucher T, Brost R, Costanzo M, Schmidt A, Aebersold R, Boone C, Hofmann K, Peter M (2009) Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA. Nature 458:228–232CrossRefPubMedGoogle Scholar
  75. 75.
    Schlieker CD, Van der Veen AG, Damon JR, Spooner E, Ploegh HL (2008) A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc Natl Acad Sci U S A 105:18255–18260CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Goehring, A.S. Rivers DM, Sprague GF Jr (2003) Urmylation: a ubiquitin-like pathway that functions during invasive growth and budding in yeast. Mol Biol Cell 14: 4329–4341Google Scholar
  77. 77.
    Humbard MA, Miranda HV, Lim JM, Krause DJ, Pritz JR, Zhou G, Chen S, Wells L, Maupin-Furlow JA (2010) Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii. Nature 463:54–60CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Darwin KH, Hofmann K (2010) SAMPyling proteins in archaea. Trends Biochem Sci 35:348–351CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Noma A, Sakaguchi Y, Suzuki T (2009) Mechanistic characterization of the sulfur-relay system for eukaryotic 2-thiouridine biogenesis at tRNA wobble positions. Nucleic Acids Res 37:1335–1352CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Goehring AS, Rivers DM, Sprague GF Jr. (2003) Attachment of the ubiquitin-related protein Urm1p to the antioxidant protein Ahp1p. Eukaryot Cell 2: 930–936Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.R&D, Consortium for Training, Research, and DevelopmentKolkataIndia
  2. 2.Department of Biochemistry, Faculty of ScienceThe Maharaja Sayajirao University of BarodaVadodaraIndia

Personalised recommendations