Machines of Destruction – AAA+ Proteases and the Adaptors That Control Them

Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 66)

Abstract

Bacteria are frequently exposed to changes in environmental conditions, such as fluctuations in temperature, pH or the availability of nutrients. These assaults can be detrimental to cell as they often result in a proteotoxic stress, which can cause the accumulation of unfolded proteins. In order to restore a productive folding environment in the cell, bacteria have evolved a network of proteins, known as the protein quality control (PQC) network, which is composed of both chaperones and AAA+ proteases. These AAA+ proteases form a major part of this PQC network, as they are responsible for the removal of unwanted and damaged proteins. They also play an important role in the turnover of specific regulatory or tagged proteins. In this review, we describe the general features of an AAA+ protease, and using two of the best-characterised AAA+ proteases in Escherichia coli (ClpAP and ClpXP) as a model for all AAA+ proteases, we provide a detailed mechanistic description of how these machines work. Specifically, the review examines the physiological role of these machines, as well as the substrates and the adaptor proteins that modulate their substrate specificity.

Keywords

Adaptor Protein Protein Quality Control Accessory Domain Axial Pore Substrate Translocation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Sauer RT, Baker TA (2011) AAA+  proteases: ATP-fueled machines of protein destruction. Annu Rev Biochem 80:587–612PubMedGoogle Scholar
  2. 2.
    Samanovic M, Li H, Darwin KH (2013) The Pup-proteasome system of Mycobacterium tuberculosis. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:267–295Google Scholar
  3. 3.
    Molière N, Turgay K (2013) General and regulatory proteolysis in Bacillus subtilis. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:73–103Google Scholar
  4. 4.
    Gur E (2013) The Lon AAA+  protease. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:35–51Google Scholar
  5. 5.
    Okuno T, Ogura T (2013) FtsH protease-mediated regulation of various cellular functions. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:53–69Google Scholar
  6. 6.
    Barchinger SE, Ades SE (2013) Regulated proteolysis: control of the Escherichia coli σE-dependent cell envelope stress response. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:129–160Google Scholar
  7. 7.
    Micevski D, Dougan DA (2013) Proteolytic regulation of stress response pathways in Escherichia coli. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:105–128Google Scholar
  8. 8.
    Frees D, Brøndsted L, Ingmer H (2013) Bacterial proteases and virulence. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:161–192Google Scholar
  9. 9.
    Kirstein-Miles J, Morimoto RI (2010) Caenorhabditis elegans as a model system to study intercompartmental proteostasis: interrelation of mitochondrial function, longevity, and neurodegenerative diseases. Dev Dyn 239(5):1529–1538PubMedGoogle Scholar
  10. 10.
    Truscott KN, Bezawork-Geleta A, Dougan DA (2011) Unfolded protein responses in bacteria and mitochondria: a central role for the ClpXP machine. IUBMB Life 63(11):955–963PubMedGoogle Scholar
  11. 11.
    Kwasniak M, Pogorzelec L, Migdal I, Smakowska E et al (2012) Proteolytic system of plant mitochondria. Physiol Plant 145(1):187–195PubMedGoogle Scholar
  12. 12.
    Truscott KN, Lowth BR, Strack PR, Dougan DA (2010) Diverse functions of mitochondrial AAA+  proteins: protein activation, disaggregation, and degradation. Biochem Cell Biol 88(1):97–108PubMedGoogle Scholar
  13. 13.
    van Dyck L, Dembowski M, Neupert W, Langer T (1998) Mcx1p, a ClpX homologue in mitochondria of Saccharomyces cerevisiae. FEBS Lett 438(3):250–254PubMedGoogle Scholar
  14. 14.
    Voos W, Ward L, Truscott KN (2013) The role of AAA+  proteases in mitochondrial protein biogenesis, homeostasis and activity control. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:223–263Google Scholar
  15. 15.
    Clarke AK (2012) The chloroplast ATP-dependent Clp protease in vascular plants – new dimensions and future challenges. Physiol Plant 145(1):235–244PubMedGoogle Scholar
  16. 16.
    Olinares PD, Kim J, van Wijk KJ (2011) The Clp protease system; a central component of the chloroplast protease network. Biochim Biophys Acta 1807(8):999–1011PubMedGoogle Scholar
  17. 17.
    Bochtler M, Hartmann C, Song HK, Bourenkov GP et al (2000) The structures of HsIU and the ATP-dependent protease HsIU-HsIV. Nature 403(6771):800–805PubMedGoogle Scholar
  18. 18.
    Sousa MC, Trame CB, Tsuruta H, Wilbanks SM et al (2000) Crystal and solution structures of an HslUV protease-chaperone complex. Cell 103(4):633–643PubMedGoogle Scholar
  19. 19.
    Maglica Z, Kolygo K, Weber-Ban E (2009) Optimal efficiency of ClpAP and ClpXP chaperone-proteases is achieved by architectural symmetry. Structure 17(4):508–516PubMedGoogle Scholar
  20. 20.
    Wang J, Hartling JA, Flanagan JM (1997) The structure of ClpP at 2.3 A resolution suggests a model for ATP-dependent proteolysis. Cell 91(4):447–456PubMedGoogle Scholar
  21. 21.
    Gribun A, Kimber MS, Ching R, Sprangers R et al (2005) The ClpP double ring tetradecameric protease exhibits plastic ring-ring interactions, and the N termini of its subunits form flexible loops that are essential for ClpXP and ClpAP complex formation. J Biol Chem 280(16):16185–16196PubMedGoogle Scholar
  22. 22.
    Sprangers R, Gribun A, Hwang PM, Houry WA et al (2005) Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release. Proc Natl Acad Sci U S A 102(46):16678–16683PubMedGoogle Scholar
  23. 23.
    Maurizi MR, Clark WP, Katayama Y, Rudikoff S et al (1990) Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli. J Biol Chem 265(21):12536–12545PubMedGoogle Scholar
  24. 24.
    Arribas J, Castano JG (1993) A comparative study of the chymotrypsin-like activity of the rat liver multicatalytic proteinase and the ClpP from Escherichia coli. J Biol Chem 268(28):21165–21171PubMedGoogle Scholar
  25. 25.
    Thompson MW, Maurizi MR (1994) Activity and specificity of Escherichia coli ClpAP protease in cleaving model peptide substrates. J Biol Chem 269(27):18201–18208PubMedGoogle Scholar
  26. 26.
    Jennings LD, Lun DS, Medard M, Licht S (2008) ClpP hydrolyzes a protein substrate processively in the absence of the ClpA ATPase: mechanistic studies of ATP-independent proteolysis. Biochemistry 47(44):11536–11546PubMedGoogle Scholar
  27. 27.
    Effantin G, Ishikawa T, De Donatis GM, Maurizi MR et al (2010) Local and global mobility in the ClpA AAA+  chaperone detected by cryo-electron microscopy: functional connotations. Structure 18(5):553–562PubMedGoogle Scholar
  28. 28.
    Jennings LD, Bohon J, Chance MR, Licht S (2008) The ClpP N-terminus coordinates substrate access with protease active site reactivity. Biochemistry 47(42):11031–11040PubMedGoogle Scholar
  29. 29.
    Li DH, Chung YS, Gloyd M, Joseph E et al (2010) Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: a model for the ClpX/ClpA-bound state of ClpP. Chem Biol 17(9):959–969PubMedGoogle Scholar
  30. 30.
    Leung E, Datti A, Cossette M, Goodreid J et al (2011) Activators of cylindrical proteases as antimicrobials: identification and development of small molecule activators of ClpP protease. Chem Biol 18(9):1167–1178PubMedGoogle Scholar
  31. 31.
    Lee BG, Park EY, Lee KE, Jeon H et al (2010) Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. Nat Struct Mol Biol 17(4):471–478PubMedGoogle Scholar
  32. 32.
    Kirstein J, Hoffmann A, Lilie H, Schmidt R et al (2009) The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease. EMBO Mol Med 1(1):37–49PubMedGoogle Scholar
  33. 33.
    Dougan DA (2011) Chemical activators of ClpP: turning Jekyll into Hyde. Chem Biol 18(9):1072–1074PubMedGoogle Scholar
  34. 34.
    Brotz-Oesterhelt H, Beyer D, Kroll HP, Endermann R et al (2005) Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat Med 11(10):1082–1087PubMedGoogle Scholar
  35. 35.
    Sass P, Josten M, Famulla K, Schiffer G et al (2011) Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ. Proc Natl Acad Sci U S A 108(42):17474–17479PubMedGoogle Scholar
  36. 36.
    Kirstein J, Schlothauer T, Dougan DA, Lilie H et al (2006) Adaptor protein controlled oligomerization activates the AAA+  protein ClpC. EMBO J 25(7):1481–1491PubMedGoogle Scholar
  37. 37.
    Lowth BR, Kirstein-Miles J, Saiyed T, Brotz-Oesterhelt H et al (2012) Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+  protein CLPX. J Struct Biol 179(2):193–201PubMedGoogle Scholar
  38. 38.
    Kang SG, Dimitrova MN, Ortega J, Ginsburg A et al (2005) Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX. J Biol Chem 280(42):35424–35432PubMedGoogle Scholar
  39. 39.
    Alexopoulos JA, Guarne A, Ortega J (2012) ClpP: a structurally dynamic protease regulated by AAA+  proteins. J Struct Biol 179(2):202–210PubMedGoogle Scholar
  40. 40.
    Dougan DA, Reid BG, Horwich AL, Bukau B (2002) ClpS, a substrate modulator of the ClpAP machine. Mol Cell 9(3):673–683PubMedGoogle Scholar
  41. 41.
    Guo F, Esser L, Singh SK, Maurizi MR et al (2002) Crystal structure of the heterodimeric complex of the adaptor, ClpS, with the N-domain of the AAA+  chaperone, ClpA. J Biol Chem 277(48):46753–46762PubMedGoogle Scholar
  42. 42.
    Zeth K, Ravelli RB, Paal K, Cusack S et al (2002) Structural analysis of the adaptor protein ClpS in complex with the N-terminal domain of ClpA. Nat Struct Biol 9(12):906–911PubMedGoogle Scholar
  43. 43.
    Erbse AH, Wagner JN, Truscott KN, Spall SK et al (2008) Conserved residues in the N-domain of the AAA+  chaperone ClpA regulate substrate recognition and unfolding. FEBS J 275(7):1400–1410PubMedGoogle Scholar
  44. 44.
    Lo JH, Baker TA, Sauer RT (2001) Characterization of the N-terminal repeat domain of Escherichia coli ClpA-A class I Clp/HSP100 ATPase. Protein Sci 10(3):551–559PubMedGoogle Scholar
  45. 45.
    Kirstein J, Dougan DA, Gerth U, Hecker M et al (2007) The tyrosine kinase McsB is a regulated adaptor protein for ClpCP. EMBO J 26(8):2061–2070PubMedGoogle Scholar
  46. 46.
    Kirstein J, Moliere N, Dougan DA, Turgay K (2009) Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+  proteases. Nat Rev Microbiol 7(8):589–599PubMedGoogle Scholar
  47. 47.
    Kojetin DJ, McLaughlin PD, Thompson RJ, Dubnau D et al (2009) Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions. J Mol Biol 387(3):639–652PubMedGoogle Scholar
  48. 48.
    Wang F, Mei Z, Qi Y, Yan C et al (2011) Structure and mechanism of the hexameric MecA-ClpC molecular machine. Nature 471(7338):331–335PubMedGoogle Scholar
  49. 49.
    Donaldson LW, Wojtyra U, Houry WA (2003) Solution structure of the dimeric zinc binding domain of the chaperone ClpX. J Biol Chem 278(49):48991–48996PubMedGoogle Scholar
  50. 50.
    Dougan DA, Weber-Ban E, Bukau B (2003) Targeted delivery of an ssrA-tagged substrate by the adaptor protein SspB to its cognate AAA+  protein ClpX. Mol Cell 12(2):373–380PubMedGoogle Scholar
  51. 51.
    Thibault G, Houry WA (2012) Role of the N-terminal domain of the chaperone ClpX in the recognition and degradation of lambda phage protein O. J Phys Chem B 116(23):6717–6724PubMedGoogle Scholar
  52. 52.
    Wojtyra UA, Thibault G, Tuite A, Houry WA (2003) The N-terminal zinc binding domain of ClpX is a dimerization domain that modulates the chaperone function. J Biol Chem 278(49):48981–48990PubMedGoogle Scholar
  53. 53.
    Park EY, Lee BG, Hong SB, Kim HW et al (2007) Structural basis of SspB-tail recognition by the zinc binding domain of ClpX. J Mol Biol 367(2):514–526PubMedGoogle Scholar
  54. 54.
    Neher SB, Sauer RT, Baker TA (2003) Distinct peptide signals in the UmuD and UmuD′ subunits of UmuD/D′ mediate tethering and substrate processing by the ClpXP protease. Proc Natl Acad Sci U S A 100(23):13219–13224PubMedGoogle Scholar
  55. 55.
    Glynn SE, Martin A, Nager AR, Baker TA et al (2009) Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+  protein-unfolding machine. Cell 139(4):744–756PubMedGoogle Scholar
  56. 56.
    Kim DY, Kim KK (2003) Crystal structure of ClpX molecular chaperone from Helicobacter pylori. J Biol Chem 278(50):50664–50670PubMedGoogle Scholar
  57. 57.
    Neuwald AF, Aravind L, Spouge JL, Koonin EV (1999) AAA+: a class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9(1):27–43PubMedGoogle Scholar
  58. 58.
    Hinnerwisch J, Fenton WA, Furtak KJ, Farr GW et al (2005) Loops in the central channel of ClpA chaperone mediate protein binding, unfolding, and translocation. Cell 121(7):1029–1041PubMedGoogle Scholar
  59. 59.
    Okuno T, Yamanaka K, Ogura T (2006) Characterization of mutants of the Escherichia coli AAA protease, FtsH, carrying a mutation in the central pore region. J Struct Biol 156(1):109–114PubMedGoogle Scholar
  60. 60.
    Schlieker C, Weibezahn J, Patzelt H, Tessarz P et al (2004) Substrate recognition by the AAA+  chaperone ClpB. Nat Struct Mol Biol 11(7):607–615PubMedGoogle Scholar
  61. 61.
    Yamada-Inagawa T, Okuno T, Karata K, Yamanaka K et al (2003) Conserved pore residues in the AAA protease FtsH are important for proteolysis and its coupling to ATP hydrolysis. J Biol Chem 278(50):50182–50187PubMedGoogle Scholar
  62. 62.
    Turgay K, Persuh M, Hahn J, Dubnau D (2001) Roles of the two ClpC ATP binding sites in the regulation of competence and the stress response. Mol Microbiol 42(3):717–727PubMedGoogle Scholar
  63. 63.
    Singh SK, Maurizi MR (1994) Mutational analysis demonstrates different functional roles for the two ATP-binding sites in ClpAP protease from Escherichia coli. J Biol Chem 269(47):29537–29545PubMedGoogle Scholar
  64. 64.
    Kress W, Mutschler H, Weber-Ban E (2009) Both ATPase domains of ClpA are critical for processing of stable protein structures. J Biol Chem 284(45):31441–31452PubMedGoogle Scholar
  65. 65.
    Hersch GL, Burton RE, Bolon DN, Baker TA et al (2005) Asymmetric interactions of ATP with the AAA+  ClpX6 unfoldase: allosteric control of a protein machine. Cell 121(7):1017–1027PubMedGoogle Scholar
  66. 66.
    Grimaud R, Kessel M, Beuron F, Steven AC et al (1998) Enzymatic and structural similarities between the Escherichia coli ATP-dependent proteases, ClpXP and ClpAP. J Biol Chem 273(20):12476–12481PubMedGoogle Scholar
  67. 67.
    Joshi SA, Hersch GL, Baker TA, Sauer RT (2004) Communication between ClpX and ClpP during substrate processing and degradation. Nat Struct Mol Biol 11(5):404–411PubMedGoogle Scholar
  68. 68.
    Kim YI, Levchenko I, Fraczkowska K, Woodruff RV et al (2001) Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase. Nat Struct Biol 8(3):230–233PubMedGoogle Scholar
  69. 69.
    Singh SK, Rozycki J, Ortega J, Ishikawa T et al (2001) Functional domains of the ClpA and ClpX molecular chaperones identified by limited proteolysis and deletion analysis. J Biol Chem 276(31):29420–29429PubMedGoogle Scholar
  70. 70.
    Bewley MC, Graziano V, Griffin K, Flanagan JM (2006) The asymmetry in the mature amino-terminus of ClpP facilitates a local symmetry match in ClpAP and ClpXP complexes. J Struct Biol 153(2):113–128PubMedGoogle Scholar
  71. 71.
    Martin A, Baker TA, Sauer RT (2007) Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+  protease. Mol Cell 27(1):41–52PubMedGoogle Scholar
  72. 72.
    Ishihama Y, Schmidt T, Rappsilber J, Mann M et al (2008) Protein abundance profiling of the Escherichia coli cytosol. BMC Genomics 9:102PubMedGoogle Scholar
  73. 73.
    Schrader EK, Harstad KG, Matouschek A (2009) Targeting proteins for degradation. Nat Chem Biol 5(11):815–822PubMedGoogle Scholar
  74. 74.
    Dougan DA, Truscott KN, Zeth K (2010) The bacterial N-end rule pathway: expect the unexpected. Mol Microbiol 76(3):545–558PubMedGoogle Scholar
  75. 75.
    Karzai AW, Roche ED, Sauer RT (2000) The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue. Nat Struct Biol 7(6):449–455PubMedGoogle Scholar
  76. 76.
    Flynn JM, Levchenko I, Sauer RT, Baker TA (2004) Modulating substrate choice: the SspB adaptor delivers a regulator of the extracytoplasmic-stress response to the AAA+  protease ClpXP for degradation. Genes Dev 18(18):2292–2301PubMedGoogle Scholar
  77. 77.
    Neher SB, Flynn JM, Sauer RT, Baker TA (2003) Latent ClpX-recognition signals ensure LexA destruction after DNA damage. Genes Dev 17(9):1084–1089PubMedGoogle Scholar
  78. 78.
    Ninnis RL, Spall SK, Talbo GH, Truscott KN et al (2009) Modification of PATase by L/F-transferase generates a ClpS-dependent N-end rule substrate in Escherichia coli. EMBO J 28(12):1732–1744PubMedGoogle Scholar
  79. 79.
    Schmidt R, Zahn R, Bukau B, Mogk A (2009) ClpS is the recognition component for Escherichia coli substrates of the N-end rule degradation pathway. Mol Microbiol 72(2):506–517PubMedGoogle Scholar
  80. 80.
    Lange R, Hengge-Aronis R (1994) The cellular concentration of the sigma S subunit of RNA polymerase in Escherichia coli is controlled at the levels of transcription, translation, and protein stability. Genes Dev 8(13):1600–1612PubMedGoogle Scholar
  81. 81.
    Lies M, Maurizi MR (2008) Turnover of endogenous SsrA-tagged proteins mediated by ATP-dependent proteases in Escherichia coli. J Biol Chem 283(34):22918–22929PubMedGoogle Scholar
  82. 82.
    Moore SD, Sauer RT (2005) Ribosome rescue: tmRNA tagging activity and capacity in Escherichia coli. Mol Microbiol 58(2):456–466PubMedGoogle Scholar
  83. 83.
    Moore SD, Sauer RT (2007) The tmRNA system for translational surveillance and ribosome rescue. Annu Rev Biochem 76:101–124PubMedGoogle Scholar
  84. 84.
    Keiler KC, Waller PR, Sauer RT (1996) Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271(5251):990–993PubMedGoogle Scholar
  85. 85.
    Oh BK, Chauhan AK, Isono K, Apirion D (1990) Location of a gene (ssrA) for a small, stable RNA (10Sa RNA) in the Escherichia coli chromosome. J Bacteriol 172(8):4708–4709PubMedGoogle Scholar
  86. 86.
    Komine Y, Kitabatake M, Yokogawa T, Nishikawa K et al (1994) A tRNA-like structure is present in 10Sa RNA, a small stable RNA from Escherichia coli. Proc Natl Acad Sci U S A 91(20):9223–9227PubMedGoogle Scholar
  87. 87.
    Tu GF, Reid GE, Zhang JG, Moritz RL et al (1995) C-terminal extension of truncated recombinant proteins in Escherichia coli with a 10Sa RNA decapeptide. J Biol Chem 270(16):9322–9326PubMedGoogle Scholar
  88. 88.
    Gottesman S, Roche E, Zhou Y, Sauer RT (1998) The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. Genes Dev 12(9):1338–1347PubMedGoogle Scholar
  89. 89.
    Gur E, Sauer RT (2008) Evolution of the ssrA degradation tag in Mycoplasma: specificity switch to a different protease. Proc Natl Acad Sci U S A 105(42):16113–16118PubMedGoogle Scholar
  90. 90.
    Herman C, Prakash S, Lu CZ, Matouschek A et al (2003) Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH. Mol Cell 11(3):659–669PubMedGoogle Scholar
  91. 91.
    Farrell CM, Grossman AD, Sauer RT (2005) Cytoplasmic degradation of ssrA-tagged proteins. Mol Microbiol 57(6):1750–1761PubMedGoogle Scholar
  92. 92.
    Kenniston JA, Baker TA, Fernandez JM, Sauer RT (2003) Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+  degradation machine. Cell 114(4):511–520PubMedGoogle Scholar
  93. 93.
    Kenniston JA, Baker TA, Sauer RT (2005) Partitioning between unfolding and release of native domains during ClpXP degradation determines substrate selectivity and partial processing. Proc Natl Acad Sci U S A 102(5):1390–1395PubMedGoogle Scholar
  94. 94.
    Kenniston JA, Burton RE, Siddiqui SM, Baker TA et al (2004) Effects of local protein stability and the geometric position of the substrate degradation tag on the efficiency of ClpXP denaturation and degradation. J Struct Biol 146(1–2):130–140PubMedGoogle Scholar
  95. 95.
    Weber-Ban EU, Reid BG, Miranker AD, Horwich AL (1999) Global unfolding of a substrate protein by the Hsp100 chaperone ClpA. Nature 401(6748):90–93PubMedGoogle Scholar
  96. 96.
    Flynn JM, Neher SB, Kim YI, Sauer RT et al (2003) Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol Cell 11(3):671–683PubMedGoogle Scholar
  97. 97.
    Neher SB, Villen J, Oakes EC, Bakalarski CE et al (2006) Proteomic profiling of ClpXP substrates after DNA damage reveals extensive instability within SOS regulon. Mol Cell 22(2):193–204PubMedGoogle Scholar
  98. 98.
    Gonciarz-Swiatek M, Wawrzynow A, Um SJ, Learn BA et al (1999) Recognition, targeting, and hydrolysis of the lambda O replication protein by the ClpP/ClpX protease. J Biol Chem 274(20):13999–14005PubMedGoogle Scholar
  99. 99.
    Farrell CM, Baker TA, Sauer RT (2007) Altered specificity of a AAA+  protease. Mol Cell 25(1):161–166PubMedGoogle Scholar
  100. 100.
    Gottesman S, Clark WP, Maurizi MR (1990) The ATP-dependent Clp protease of Escherichia coli. Sequence of clpA and identification of a Clp-specific substrate. J Biol Chem 265(14):7886–7893PubMedGoogle Scholar
  101. 101.
    Maglica Z, Striebel F, Weber-Ban E (2008) An intrinsic degradation tag on the ClpA C-terminus regulates the balance of ClpAP complexes with different substrate specificity. J Mol Biol 384(2):503–511PubMedGoogle Scholar
  102. 102.
    Hoskins JR, Singh SK, Maurizi MR, Wickner S (2000) Protein binding and unfolding by the chaperone ClpA and degradation by the protease ClpAP. Proc Natl Acad Sci U S A 97(16):8892–8897PubMedGoogle Scholar
  103. 103.
    Hoskins JR, Wickner S (2006) Two peptide sequences can function cooperatively to facilitate binding and unfolding by ClpA and degradation by ClpAP. Proc Natl Acad Sci U S A 103(4):909–914PubMedGoogle Scholar
  104. 104.
    Hoskins JR, Kim SY, Wickner S (2000) Substrate recognition by the ClpA chaperone component of ClpAP protease. J Biol Chem 275(45):35361–35367PubMedGoogle Scholar
  105. 105.
    Wang KH, Oakes ES, Sauer RT, Baker TA (2008) Tuning the strength of a bacterial N-end rule degradation signal. J Biol Chem 283(36):24600–24607PubMedGoogle Scholar
  106. 106.
    Kim YI, Burton RE, Burton BM, Sauer RT et al (2000) Dynamics of substrate denaturation and translocation by the ClpXP degradation machine. Mol Cell 5(4):639–648PubMedGoogle Scholar
  107. 107.
    Martin A, Baker TA, Sauer RT (2008) Pore loops of the AAA+  ClpX machine grip substrates to drive translocation and unfolding. Nat Struct Mol Biol 15(11):1147–1151PubMedGoogle Scholar
  108. 108.
    Martin A, Baker TA, Sauer RT (2008) Diverse pore loops of the AAA+  ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates. Mol Cell 29(4):441–450PubMedGoogle Scholar
  109. 109.
    Park E, Rho YM, Koh OJ, Ahn SW et al (2005) Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation for degradation by HslV peptidase. J Biol Chem 280(24):22892–22898PubMedGoogle Scholar
  110. 110.
    Hou JY, Sauer RT, Baker TA (2008) Distinct structural elements of the adaptor ClpS are required for regulating degradation by ClpAP. Nat Struct Mol Biol 15(3):288–294PubMedGoogle Scholar
  111. 111.
    Roman-Hernandez G, Hou JY, Grant RA, Sauer RT et al (2011) The ClpS adaptor mediates staged delivery of N-end rule substrates to the AAA+  ClpAP protease. Mol Cell 43(2):217–228PubMedGoogle Scholar
  112. 112.
    Levchenko I, Seidel M, Sauer RT, Baker TA (2000) A specificity-enhancing factor for the ClpXP degradation machine. Science 289(5488):2354–2356PubMedGoogle Scholar
  113. 113.
    Zhou Y, Gottesman S, Hoskins JR, Maurizi MR et al (2001) The RssB response regulator directly targets sigma(S) for degradation by ClpXP. Genes Dev 15(5):627–637PubMedGoogle Scholar
  114. 114.
    Erbse A, Schmidt R, Bornemann T, Schneider-Mergener J et al (2006) ClpS is an essential component of the N-end rule pathway in Escherichia coli. Nature 439(7077):753–756PubMedGoogle Scholar
  115. 115.
    Muffler A, Fischer D, Altuvia S, Storz G et al (1996) The response regulator RssB controls stability of the sigma(S) subunit of RNA polymerase in Escherichia coli. EMBO J 15(6):1333–1339PubMedGoogle Scholar
  116. 116.
    Pratt LA, Silhavy TJ (1996) The response regulator SprE controls the stability of RpoS. Proc Natl Acad Sci U S A 93(6):2488–2492PubMedGoogle Scholar
  117. 117.
    Elsholz AK, Turgay K, Michalik S, Hessling B et al (2012) Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis. Proc Natl Acad Sci U S A 109(19):7451–7456PubMedGoogle Scholar
  118. 118.
    Fuhrmann J, Schmidt A, Spiess S, Lehner A et al (2009) McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR. Science 324(5932):1323–1327PubMedGoogle Scholar
  119. 119.
    Persuh M, Mandic-Mulec I, Dubnau D (2002) A MecA paralog, YpbH, binds ClpC, affecting both competence and sporulation. J Bacteriol 184(8):2310–2313PubMedGoogle Scholar
  120. 120.
    Schlothauer T, Mogk A, Dougan DA, Bukau B et al (2003) MecA, an adaptor protein necessary for ClpC chaperone activity. Proc Natl Acad Sci U S A 100(5):2306–2311PubMedGoogle Scholar
  121. 121.
    Turgay K, Hahn J, Burghoorn J, Dubnau D (1998) Competence in Bacillus subtilis is controlled by regulated proteolysis of a transcription factor. EMBO J 17(22):6730–6738PubMedGoogle Scholar
  122. 122.
    Chan CM, Garg S, Lin AA, Zuber P (2012) Geobacillus thermodenitrificans YjbH recognizes the C-terminal end of Bacillus subtilis Spx to accelerate Spx proteolysis by ClpXP. Microbiology 158(Pt 5):1268–1278PubMedGoogle Scholar
  123. 123.
    Nakano MM, Nakano S, Zuber P (2002) Spx (YjbD), a negative effector of competence in Bacillus subtilis, enhances ClpC-MecA-ComK interaction. Mol Microbiol 44(5):1341–1349PubMedGoogle Scholar
  124. 124.
    Chien P, Grant RA, Sauer RT, Baker TA (2007) Structure and substrate specificity of an SspB ortholog: design implications for AAA+  adaptors. Structure 15(10):1296–1305PubMedGoogle Scholar
  125. 125.
    Lessner FH, Venters BJ, Keiler KC (2007) Proteolytic adaptor for transfer-messenger RNA-tagged proteins from alpha-proteobacteria. J Bacteriol 189(1):272–275PubMedGoogle Scholar
  126. 126.
    Levchenko I, Grant RA, Wah DA, Sauer RT et al (2003) Structure of a delivery protein for an AAA+  protease in complex with a peptide degradation tag. Mol Cell 12(2):365–372PubMedGoogle Scholar
  127. 127.
    Wah DA, Levchenko I, Rieckhof GE, Bolon DN et al (2003) Flexible linkers leash the substrate binding domain of SspB to a peptide module that stabilizes delivery complexes with the AAA+  ClpXP protease. Mol Cell 12(2):355–363PubMedGoogle Scholar
  128. 128.
    Bolon DN, Grant RA, Baker TA, Sauer RT (2004) Nucleotide-dependent substrate handoff from the SspB adaptor to the AAA+  ClpXP protease. Mol Cell 16(3):343–350PubMedGoogle Scholar
  129. 129.
    Bolon DN, Wah DA, Hersch GL, Baker TA et al (2004) Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery: a protein-design study. Mol Cell 13(3):443–449PubMedGoogle Scholar
  130. 130.
    Flynn JM, Levchenko I, Seidel M, Wickner SH et al (2001) Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis. Proc Natl Acad Sci U S A 98(19):10584–10589PubMedGoogle Scholar
  131. 131.
    McGinness KE, Baker TA, Sauer RT (2006) Engineering controllable protein degradation. Mol Cell 22(5):701–707PubMedGoogle Scholar
  132. 132.
    Becker G, Klauck E, Hengge-Aronis R (1999) Regulation of RpoS proteolysis in Escherichia coli: the response regulator RssB is a recognition factor that interacts with the turnover element in RpoS. Proc Natl Acad Sci U S A 96(11):6439–6444PubMedGoogle Scholar
  133. 133.
    Jonczyk P, Nowicka A (1996) Specific in vivo protein-protein interactions between Escherichia coli SOS mutagenesis proteins. J Bacteriol 178(9):2580–2585PubMedGoogle Scholar
  134. 134.
    Gonzalez M, Rasulova F, Maurizi MR, Woodgate R (2000) Subunit-specific degradation of the UmuD/D′ heterodimer by the ClpXP protease: the role of trans recognition in UmuD′ stability. EMBO J 19(19):5251–5258PubMedGoogle Scholar
  135. 135.
    Varshavsky A (1996) The N-end rule: functions, mysteries, uses. Proc Natl Acad Sci U S A 93(22):12142–12149PubMedGoogle Scholar
  136. 136.
    Varshavsky A (2011) The N-end rule pathway and regulation by proteolysis. Protein Sci 20(8):1298–1345Google Scholar
  137. 137.
    Dougan DA, Micevski D, Truscott KN (2012) The N-end rule pathway: from recognition by N-recognins, to destruction by AAA+  proteases. Biochim Biophys Acta 1823(1):83–91PubMedGoogle Scholar
  138. 138.
    Graciet E, Wellmer F (2010) The plant N-end rule pathway: structure and functions. Trends Plant Sci 15(8):447–453PubMedGoogle Scholar
  139. 139.
    Mogk A, Schmidt R, Bukau B (2007) The N-end rule pathway for regulated proteolysis: prokaryotic and eukaryotic strategies. Trends Cell Biol 17(4):165–172PubMedGoogle Scholar
  140. 140.
    Shrader TE, Tobias JW, Varshavsky A (1993) The N-end rule in Escherichia coli: cloning and analysis of the leucyl, phenylalanyl-tRNA-protein transferase gene aat. J Bacteriol 175(14):4364–4374PubMedGoogle Scholar
  141. 141.
    Lupas AN, Koretke KK (2003) Bioinformatic analysis of ClpS, a protein module involved in prokaryotic and eukaryotic protein degradation. J Struct Biol 141(1):77–83PubMedGoogle Scholar
  142. 142.
    Roman-Hernandez G, Grant RA, Sauer RT, Baker TA (2009) Molecular basis of substrate selection by the N-end rule adaptor protein ClpS. Proc Natl Acad Sci U S A 106(22):8888–8893PubMedGoogle Scholar
  143. 143.
    Schuenemann VJ, Kralik SM, Albrecht R, Spall SK et al (2009) Structural basis of N-end rule substrate recognition in Escherichia coli by the ClpAP adaptor protein ClpS. EMBO Rep 10(5):508–514PubMedGoogle Scholar
  144. 144.
    Wang KH, Roman-Hernandez G, Grant RA, Sauer RT et al (2008) The molecular basis of N-end rule recognition. Mol Cell 32(3):406–414PubMedGoogle Scholar
  145. 145.
    Turgay K, Hamoen LW, Venema G, Dubnau D (1997) Biochemical characterization of a molecular switch involving the heat shock protein ClpC, which controls the activity of ComK, the competence transcription factor of Bacillus subtilis. Genes Dev 11(1):119–128PubMedGoogle Scholar
  146. 146.
    Persuh M, Turgay K, Mandic-Mulec I, Dubnau D (1999) The N- and C-terminal domains of MecA recognize different partners in the competence molecular switch. Mol Microbiol 33(4):886–894PubMedGoogle Scholar
  147. 147.
    Andersson FI, Blakytny R, Kirstein J, Turgay K et al (2006) Cyanobacterial ClpC/HSP100 protein displays intrinsic chaperone activity. J Biol Chem 281(9):5468–5475PubMedGoogle Scholar
  148. 148.
    Burton RE, Siddiqui SM, Kim YI, Baker TA et al (2001) Effects of protein stability and structure on substrate processing by the ClpXP unfolding and degradation machine. EMBO J 20(12):3092–3100PubMedGoogle Scholar
  149. 149.
    Reid BG, Fenton WA, Horwich AL, Weber-Ban EU (2001) ClpA mediates directional translocation of substrate proteins into the ClpP protease. Proc Natl Acad Sci U S A 98(7):3768–3772PubMedGoogle Scholar
  150. 150.
    Wang J, Song JJ, Seong IS, Franklin MC et al (2001) Nucleotide-dependent conformational changes in a protease-associated ATPase HsIU. Structure 9(11):1107–1116PubMedGoogle Scholar
  151. 151.
    Farr GW, Furtak K, Rowland MB, Ranson NA et al (2000) Multivalent binding of nonnative substrate proteins by the chaperonin GroEL. Cell 100(5):561–573PubMedGoogle Scholar
  152. 152.
    Martin A, Baker TA, Sauer RT (2005) Rebuilt AAA+  motors reveal operating principles for ATP-fuelled machines. Nature 437(7062):1115–1120PubMedGoogle Scholar
  153. 153.
    Li H, Carrion-Vazquez M, Oberhauser AF, Marszalek PE et al (2000) Point mutations alter the mechanical stability of immunoglobulin modules. Nat Struct Biol 7(12):1117–1120PubMedGoogle Scholar
  154. 154.
    Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA et al (2011) Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell 145(2):257–267PubMedGoogle Scholar
  155. 155.
    Lee C, Schwartz MP, Prakash S, Iwakura M et al (2001) ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal. Mol Cell 7(3):627–637PubMedGoogle Scholar
  156. 156.
    Barkow SR, Levchenko I, Baker TA, Sauer RT (2009) Polypeptide translocation by the AAA+  ClpXP protease machine. Chem Biol 16(6):605–612PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Life Sciences DepartmentBen-Gurion University of the NegevBeer-ShevaIsrael
  2. 2.The National Institute for Biotechnology in the NegevBeer-ShevaIsrael
  3. 3.Department for Biochemistry, La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneAustralia

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