1932

Abstract

Regulated proteolysis is a vital process that affects all living things. Bacteria use energy-dependent AAA+ proteases to power degradation of misfolded and native regulatory proteins. Given that proteolysis is an irreversible event, specificity and selectivity in degrading substrates are key. Specificity is often augmented through the use of adaptors that modify the inherent specificity of the proteolytic machinery. Regulated protein degradation is intricately linked to quality control, cell-cycle progression, and physiological transitions. In this review, we highlight recent work that has shed light on our understanding of regulated proteolysis in bacteria. We discuss the role AAA+ proteases play during balanced growth as well as how these proteases are deployed during changes in growth. We present examples of how protease selectivity can be controlled in increasingly complex ways. Finally, we describe how coupling a core recognition determinant to one or more modifying agents is a general theme for regulated protein degradation.

Keyword(s): AAA+ proteasesClpPClpXLon
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-062917-012848
2018-06-20
2024-05-20
Loading full text...

Full text loading...

/deliver/fulltext/biochem/87/1/annurev-biochem-062917-012848.html?itemId=/content/journals/10.1146/annurev-biochem-062917-012848&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Strieter ER, Korasick DA 2012. Unraveling the complexity of ubiquitin signaling. ACS Chem. Biol. 7:152–63
    [Google Scholar]
  2. 2.  Gur E, Biran D, Ron EZ 2011. Regulated proteolysis in Gram-negative bacteria—how and when?. Nat. Rev. Microbiol. 9:12839–48
    [Google Scholar]
  3. 3.  Olivares AO, Baker TA, Sauer RT 2016. Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines. Nat. Rev. Microbiol. 14:133–44
    [Google Scholar]
  4. 4.  Gottesman S. 1996. Proteases and their targets in Escherichia coli. Annu. Rev. Genet 30:465–506
    [Google Scholar]
  5. 5.  Breidenstein EBM, Janot L, Strehmel J, Fernandez L, Taylor PK et al. 2012. The Lon protease is essential for full virulence in Pseudomonas aeruginosa. PLOS ONE 7:11e49123
    [Google Scholar]
  6. 6.  Kanemori M, Nishihara K, Yanagi H, Yura T 1997. Synergistic roles of Hs1VU and other ATP-dependent proteases in controlling in vivo turnover of σ32 and abnormal proteins in Escherichia coli. J. Bacteriol 179:237219–25
    [Google Scholar]
  7. 7.  Howard-Flanders P, Simson E, Theriot L 1964. A locus that controls filament formation and sensitivity to radiation in Escherichia coli K-12. Genetics 49:237–46
    [Google Scholar]
  8. 8.  Jenal U, Fuchs T 1998. An essential protease involved in bacterial cell-cycle control. EMBO J 17:195658–69
    [Google Scholar]
  9. 9.  Rogers A, Townsley L, Gallego-Hernandez AL, Beyhan S, Kwuan L, Yildiz FH 2016. The LonA protease regulates biofilm formation, motility, virulence, and the type VI secretion system in Vibrio cholerae. J. Bacteriol 198:6973–85
    [Google Scholar]
  10. 10.  Baker TA, Sauer RT 2006. ATP-dependent proteases of bacteria: recognition logic and operating principles. Trends Biochem. Sci. 31:12647–53
    [Google Scholar]
  11. 11.  Lee I, Suzuki CK 2008. Functional mechanics of the ATP-dependent Lon protease—lessons from endogenous protein and synthetic peptide substrates. Biochim. Biophys. Acta 1784:5727–35
    [Google Scholar]
  12. 12.  Langklotz S, Baumann U, Narberhaus F 2012. Structure and function of the bacterial AAA protease FtsH. Biochim. Biophys. Acta 1823:140–48
    [Google Scholar]
  13. 13.  Baker TA, Sauer RT 2012. ClpXP, an ATP-powered unfolding and protein-degradation machine. Biochim. Biophys. Acta 1823:115–28
    [Google Scholar]
  14. 14.  Gottesman S. 2003. Proteolysis in bacterial regulatory circuits. Annu. Rev. Cell Dev. Biol. 19:1565–87
    [Google Scholar]
  15. 15.  Rawlings ND, Barrett AJ, Finn R 2016. Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res 44:D1D343–50
    [Google Scholar]
  16. 16.  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 114:4511–20
    [Google Scholar]
  17. 17.  Kraut DA. 2013. Slippery substrates impair ATP-dependent protease function by slowing unfolding. J. Biol. Chem. 288:4834729–35
    [Google Scholar]
  18. 18.  Vass RH, Chien P 2013. Critical clamp loader processing by an essential AAA+ protease in Caulobacter crescentus. PNAS 110:4518138–43
    [Google Scholar]
  19. 19.  Koodithangal P, Jaffe NE, Kraut DA, Fishbain S, Herman C, Matouschek A 2009. ATP-dependent proteases differ substantially in their ability to unfold globular proteins. J. Biol. Chem. 284:2818674–84
    [Google Scholar]
  20. 20.  Olivares AO, Nager AR, Iosefson O, Sauer RT, Baker TA 2014. Mechanochemical basis of protein degradation by a double-ring AAA+ machine. Nat. Struct. Mol. Biol. 21:10871–75
    [Google Scholar]
  21. 21.  Maillard RA, Chistol G, Sen M, Righini M, Tan J et al. 2011. ClpX(P) generates mechanical force to unfold and translocate its protein substrates. Cell 145:3459–69
    [Google Scholar]
  22. 22.  Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ 2011. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell 145:2257–67
    [Google Scholar]
  23. 23.  Konovalova A, Søgaard-Andersen L, Kroos L 2014. Regulated proteolysis in bacterial development. FEMS Microbiol. Rev. 38:3493–522
    [Google Scholar]
  24. 24.  Mogk A, Huber D, Bukau B 2011. Integrating protein homeostasis strategies in prokaryotes. Cold Spring Harb. Perspect. Biol. 3:41–19
    [Google Scholar]
  25. 25.  Bezawork-Geleta A, Brodie EJ, Dougan DA, Truscott KN 2015. LON is the master protease that protects against protein aggregation in human mitochondria through direct degradation of misfolded proteins. Sci. Rep. 5:October17397
    [Google Scholar]
  26. 26.  Van Melderen L, Aertsen A 2009. Regulation and quality control by Lon-dependent proteolysis. Res. Microbiol. 160:9645–51
    [Google Scholar]
  27. 27.  Chung CH, Goldberg AL 1981. The product of the lon (capR) gene in Escherichia coli is the ATP-dependent protease, protease La. PNAS 78:84931–35
    [Google Scholar]
  28. 28.  Flynn JM, Levchenko I, Seidel M, Wickner SH, Sauer RT, Baker TA 2001. Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis. PNAS 98:1910584–89
    [Google Scholar]
  29. 29.  Flynn JM, Neher SB, Kim YI, Sauer RT, Baker TA 2003. Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol. Cell 11:3671–83
    [Google Scholar]
  30. 30.  Keiler KC, Waller PRH, Sauer RT 1996. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271:5251990–93
    [Google Scholar]
  31. 31.  Keiler KC. 2015. Mechanisms of ribosome rescue in bacteria. Nat. Rev. Microbiol. 13:5285–97
    [Google Scholar]
  32. 32.  Li X, Yagi M, Morita T, Aiba H 2008. Cleavage of mRNAs and role of tmRNA system under amino acid starvation in Escherichia coli. Mol. Microbiol 68:2462–73
    [Google Scholar]
  33. 33.  Christensen SK, Pedersen K, Hansen FG, Gerdes K 2003. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA. J. Mol. Biol. 332:4809–19
    [Google Scholar]
  34. 34.  Levchenko I, Seidel M, Sauer RT, Baker TA 2000. A specificity-enhancing factor for the ClpXP degradation machine. Science 289:54882354–56
    [Google Scholar]
  35. 35.  Bolon DN, Wah DA, Hersch GL, Baker TA, Sauer RT 2004. Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery: a protein-design study. Mol. Cell 13:3443–49
    [Google Scholar]
  36. 36.  Levchenko I, Grant RA, Flynn JM, Sauer RT, Baker TA 2005. Versatile modes of peptide recognition by the AAA+ adaptor protein SspB. Nat. Struct. Mol. Biol. 12:6520–25
    [Google Scholar]
  37. 37.  Lau J, Hernandez-Alicea L, Vass RH, Chien P 2015. A phosphosignaling adaptor primes the AAA+ protease ClpXP to drive cell cycle-regulated proteolysis. Mol. Cell 59:1104–16
    [Google Scholar]
  38. 38.  Joshi KK, Bergé M, Radhakrishnan SK, Viollier PH, Chien P 2015. An adaptor hierarchy regulates proteolysis during a bacterial cell cycle. Cell 163:2419–31
    [Google Scholar]
  39. 39.  Puri N, Karzai AW 2017. HspQ functions as a unique specificity-enhancing factor for the AAA+ Lon protease. Mol. Cell 66:5672–83.e4
    [Google Scholar]
  40. 40.  Gur E, Sauer RT 2008. Recognition of misfolded proteins by Lon, a AAA+ protease. Genes Dev 22:162267–77
    [Google Scholar]
  41. 41.  Gur E. 2013. The Lon AAA+ protease. Subcell. Biochem. 66:35–51
    [Google Scholar]
  42. 42.  Arndt V, Rogon C, Höhfeld J 2007. To be, or not to be—molecular chaperones in protein degradation. Cell. Mol. Life Sci. 64:19–202525–41
    [Google Scholar]
  43. 43.  Van Melderen L, Hoa M, Thi D, Lecchi P, Gottesman S et al. 1996. ATP-dependent degradation of CcdA by Lon protease. J. Biol. Chem. 271:4427730–38
    [Google Scholar]
  44. 44.  Kunová N, Ondrovičová G, Bauer JA, Bellová J, Ambro L' et al. 2017. The role of Lon-mediated proteolysis in the dynamics of mitochondrial nucleic acid-protein complexes. Sci. Rep. 7:1631
    [Google Scholar]
  45. 45.  Lu B, Lee J, Nie X, Li M, Morozov YI et al. 2013. Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Mol. Cell 49:1121–32
    [Google Scholar]
  46. 46.  Kubik S, Wegrzyn K, Pierechod M, Konieczny I 2012. Opposing effects of DNA on proteolysis of a replication initiator. Nucleic Acids Res 40:31148–59
    [Google Scholar]
  47. 47.  Ambro L, Pevala V, Bauer J, Kutejová E 2012. The influence of ATP-dependent proteases on a variety of nucleoid-associated processes. J. Struct. Biol. 179:2181–92
    [Google Scholar]
  48. 48.  Karlowicz A, Wegrzyn K, Gross M, Kaczynska D, Ropelewska M et al. 2017. Defining the crucial domain and amino acid residues in bacterial Lon protease for DNA binding and processing of DNA-interacting substrates. J. Biol. Chem. 292:187507–18
    [Google Scholar]
  49. 49.  Chung CH, Goldberg AL 1982. DNA stimulates ATP-dependent proteolysis and protein-dependent ATPase activity of protease La from Escherichia coli. PNAS 79:3795–99
    [Google Scholar]
  50. 50.  Waxman L, Goldberg AL 1986. Selectivity of intracellular proteolysis: protein substrates activate the ATP-dependent protease (La). Science 232:4749500–503
    [Google Scholar]
  51. 51.  Gur E, Sauer RT 2009. Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine. PNAS 106:4418503–8
    [Google Scholar]
  52. 52.  Jonas K, Liu J, Chien P, Laub MT 2013. Proteotoxic stress induces a cell-cycle arrest by stimulating Lon to degrade the replication initiator DnaA. Cell 154:3623–36
    [Google Scholar]
  53. 53.  Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L 2004. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol. Microbiol. 51:61705–17
    [Google Scholar]
  54. 54.  Vodermaier HC. 2004. APC/C and SCF: controlling each other and the cell cycle. Curr. Biol. 14:18787–96
    [Google Scholar]
  55. 55.  Skerker JM, Laub MT 2004. Cell-cycle progression and the generation of asymmetry in Caulobacter crescentus. Nat. Rev. Microbiol 2:4325–37
    [Google Scholar]
  56. 56.  Joshi KK, Chien P 2016. Regulated proteolysis in bacteria: Caulobacter. Annu. Rev. Genet 50:423–45
    [Google Scholar]
  57. 57.  Quon KC, Marczynski GT, Shapiro L 1996. Cell cycle control by an essential bacterial two-component signal transduction protein. Cell 84:183–93
    [Google Scholar]
  58. 58.  Quon KC, Yang B, Domian IJ, Shapiro L, Marczynski GT 1998. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. PNAS 95:1120–25
    [Google Scholar]
  59. 59.  Laub MT, Chen SL, Shapiro L, McAdams HH 2002. Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle. PNAS 99:74632–37
    [Google Scholar]
  60. 60.  Lori C, Ozaki S, Steiner S, Böhm R, Abel S et al. 2015. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature 523:7559236–39
    [Google Scholar]
  61. 61.  Biondi EG, Reisinger SJ, Skerker JM, Arif M, Perchuk BS et al. 2006. Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature 444:7121899–904
    [Google Scholar]
  62. 62.  Iniesta AA, McGrath PT, Reisenauer A, McAdams HH, Shapiro L 2006. A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression. PNAS 103:2910935–40
    [Google Scholar]
  63. 63.  Domian IJ, Quon KC, Shapiro L 1997. Cell-type specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle. Cell 90:415–24
    [Google Scholar]
  64. 64.  McGrath PT, Iniesta AA, Ryan KR, Shapiro L, McAdams HH 2006. A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell 124:3535–47
    [Google Scholar]
  65. 65.  Chien P, Perchuk BS, Laub MT, Sauer RT, Baker TA 2007. Direct and adaptor-mediated substrate recognition by an essential AAA+ protease. PNAS 104:166590–95
    [Google Scholar]
  66. 66.  Smith SC, Joshi KK, Zik JJ, Trinh K, Kamajaya A et al. 2014. Cell cycle-dependent adaptor complex for ClpXP-mediated proteolysis directly integrates phosphorylation and second messenger signals. PNAS 111:3914229–34
    [Google Scholar]
  67. 67.  Gora KG, Cantin A, Wohlever M, Joshi KK, Perchuk BS et al. 2013. Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus. Mol. Microbiol 87:61277–89
    [Google Scholar]
  68. 68.  Siam R, Marczynski GT 2000. Cell cycle regulator phosphorylation stimulates two distinct modes of binding at a chromosome replication origin. EMBO J 19:51138–47
    [Google Scholar]
  69. 69.  Haeusser DP, Lee AH, Weart RB, Levin PA 2009. ClpX inhibits FtsZ assembly in a manner that does not require its ATP hydrolysis-dependent chaperone activity. J. Bacteriol. 191:61986–91
    [Google Scholar]
  70. 70.  Camberg JL, Hoskins JR, Wickner S 2009. ClpXP protease degrades the cytoskeletal protein, FtsZ, and modulates FtsZ polymer dynamics. PNAS 106:2610614–19
    [Google Scholar]
  71. 71.  Camberg JL, Hoskins JR, Wickner S 2011. The interplay of ClpXP with the cell division machinery in Escherichia coli. J. Bacteriol 193:81911–18
    [Google Scholar]
  72. 72.  Williams B, Bhat N, Chien P, Shapiro L 2014. ClpXP and ClpAP proteolytic activity on divisome substrates is differentially regulated following the Caulobacter asymmetric cell division. Mol. Microbiol. 93:5853–66
    [Google Scholar]
  73. 73.  Bhat NH, Vass RH, Stoddard PR, Shin DK, Chien P 2013. Identification of ClpP substrates in Caulobacter crescentus reveals a role for regulated proteolysis in bacterial development. Mol. Microbiol. 88:61083–92
    [Google Scholar]
  74. 74.  Michalik S, Bernhardt J, Otto A, Moche M, Becher D et al. 2012. Life and death of proteins: a case study of glucose-starved Staphylococcus aureus. Mol. Cell. Proteom 11:9558–70
    [Google Scholar]
  75. 75.  Abel S, Chien P, Wassmann P, Schirmer T, Kaever V et al. 2011. Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks. Mol. Cell 43:4550–60
    [Google Scholar]
  76. 76.  Folcher M, Nicollier M, Schwede T, Amiot N, Duerig A 2009. Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes Dev 23:93–104
    [Google Scholar]
  77. 77.  Beaufay F, Coppine J, Mayard A, Laloux G, Bolle X De, Hallez R 2015. A NAD-dependent glutamate dehydrogenase coordinates metabolism with cell division in Caulobacter crescentus. EMBO J 34:131786–1800
    [Google Scholar]
  78. 78.  Radhakrishnan SK, Pritchard S, Viollier PH 2010. Coupling prokaryotic cell fate and division control with a bifunctional and oscillating oxidoreductase homolog. Dev. Cell 18:190–101
    [Google Scholar]
  79. 79.  Ozaki S, Schalch-Moser A, Zumthor L, Manfredi P, Ebbensgaard A et al. 2014. Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control. Mol. Microbiol. 94:3580–94
    [Google Scholar]
  80. 80.  Curtis PD, Brun YV 2014. Identification of essential alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems. Mol. Microbiol. 93:4713–35
    [Google Scholar]
  81. 81.  Hersch GL, Baker TA, Sauer RT 2004. SspB delivery of substrates for ClpXP proteolysis probed by the design of improved degradation tags. PNAS 101:3312136–41
    [Google Scholar]
  82. 82.  Cordova JC, Olivares AO, Shin Y, Stinson BM, Calmat S et al. 2014. Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine. Cell 158:3647–58
    [Google Scholar]
  83. 83.  Chan CM, Hahn E, Zuber P 2014. Adaptor bypass mutations of Bacillus subtilis spx suggest a mechanism for YjbH-enhanced proteolysis of the regulator Spx by ClpXP. Mol. Microbiol. 93:3426–38
    [Google Scholar]
  84. 84.  Stüdemann A, Noirclerc-Savoye M, Klauck E, Becker G, Schneider D, Hengge R 2003. Sequential recognition of two distinct sites in σS by the proteolytic targeting factor RssB and ClpX. EMBO J 22:164111–20
    [Google Scholar]
  85. 85.  Zhou Y, Gottesman S, Hoskins JR, Maurizi MR, Wickner S 2001. The RssB response regulator directly targets σS for degradation by ClpXP. Genes Dev 15:5627–37
    [Google Scholar]
  86. 86.  Hengge R. 2009. Proteolysis of σS (RpoS) and the general stress response in Escherichia coli. Res. Microbiol 160:9667–76
    [Google Scholar]
  87. 87.  Jishage M, Ishihama A 1995. Regulation of RNA polymerase sigma subunit synthesis in Escherichia coli: intracellular levels of sigma 70 and sigma 38. J. Bacteriol. 177:236832–35
    [Google Scholar]
  88. 88.  Pratt LA, Silhavy TJ 1996. The response regulator SprE controls the stability of RpoS. PNAS 93:62488–92
    [Google Scholar]
  89. 89.  Muffler A, Fischer D, Altuvia S, Storz G, Hengge-Aronis R 1996. The response regulator RssB controls stability of the sigma(S) subunit of RNA polymerase in Escherichia coli. EMBO J 15:61333–39
    [Google Scholar]
  90. 90.  Micevski D, Zammit JE, Truscott KN, Dougan DA 2015. Anti-adaptors use distinct modes of binding to inhibit the RssB-dependent turnover of RpoS (σS) by ClpXP. Front. Mol. Biosci. 2:April15
    [Google Scholar]
  91. 91.  Battesti A, Hoskins JR, Tong S, Milanesio P, Mann JM et al. 2013. Anti-adaptors provide multiple modes for regulation of the RssB adaptor protein. Genes Dev 27:242722–35
    [Google Scholar]
  92. 92.  Tan IS, Weiss CA, Popham DL, Ramamurthi KS 2015. A quality-control mechanism removes unfit cells from a population of sporulating bacteria. Dev. Cell 34:6682–93
    [Google Scholar]
  93. 93.  Mukherjee S, Bree AC, Liu J, Patrick JE, Chien P, Kearns DB 2014. Adaptor-mediated Lon proteolysis restricts Bacillus subtilis hyperflagellation. PNAS 112:1250–55
    [Google Scholar]
  94. 94.  Efeyan A, Comb WC, Sabatini DM 2015. Nutrient-sensing mechanisms and pathways. Nature 517:7534302–10
    [Google Scholar]
  95. 95.  Suraweera A, Münch C, Hanssum A, Bertolotti A 2012. Failure of amino acid homeostasis causes cell death following proteasome inhibition. Mol. Cell 48:2242–53
    [Google Scholar]
  96. 96.  Mandelstam J. 1957. Turnover of protein in starved bacteria and its relationship to the induced synthesis of enzyme. Nature 179:1179–81
    [Google Scholar]
  97. 97.  Hauryliuk V, Atkinson GC, Murakami KS, Tenson T, Gerdes K 2015. Recent functional insights into the role of (p)ppGpp in bacterial physiology. Nat. Rev. Microbiol. 13:5298–309
    [Google Scholar]
  98. 98.  Srivatsan A, Wang JD 2008. Control of bacterial transcription, translation and replication by (p)ppGpp. Curr. Opin. Microbiol. 11:2100–5
    [Google Scholar]
  99. 99.  Kuroda A, Murphy H, Cashel M, Kornberg A 1997. Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli. J. Biol. Chem 272:3421240–43
    [Google Scholar]
  100. 100.  Kuroda A. 2001. Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli. Science 293:5530705–8
    [Google Scholar]
  101. 101.  Nomura K, Kato J, Takiguchi N, Ohtake H, Kuroda A 2004. Effects of inorganic polyphosphate on the proteolytic and DNA-binding activities of Lon in Escherichia coli. J. Biol. Chem 279:3334406–10
    [Google Scholar]
  102. 102.  Nomura K, Kato J, Takiguchi N, Ohtake H, Kuroda A 2006. Inorganic polyphosphate stimulates Lon-mediated proteolysis of nucleoid proteins in Escherichia coli. Cell Mol. Biol 52:423–29
    [Google Scholar]
  103. 103.  Osbourne DO, Soo VW, Konieczny I, Wood TK 2014. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity. Bioengineered 5:4264–68
    [Google Scholar]
  104. 104.  Reeve CA, Bockman AT, Matin A 1984. Role of protein degradation in the survival of carbon-starved Escherichia coli and Salmonella typhimurium. J. Bacteriol. 157:3758–63
    [Google Scholar]
  105. 105.  Damerau K, John ACS 1993. Role of Clp protease subunits in degradation of carbon starvation proteins in Escherichia coli. J. Bacteriol 175:153–63
    [Google Scholar]
  106. 106.  Fetzer C, Korotkov VS, Thänert R, Lee KM, Neuenschwander M et al. 2017. A chemical disruptor of the ClpX chaperone complex attenuates multiresistant Staphylococcus aureus virulence. Angew. Chemie 56:15746–50
    [Google Scholar]
  107. 107.  Compton CL, Schmitz KR, Sauer RT, Sello JK 2013. Antibacterial activity of and resistance to small molecule inhibitors of the ClpP peptidase. ACS Chem. Biol. 8:122669–77
    [Google Scholar]
  108. 108.  Famulla K, Sass P, Malik I, Akopian T, Kandror O et al. 2016. Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease. Mol. Microbiol. 101:2194–209
    [Google Scholar]
  109. 109.  Conlon BP, Nakayasu ES, Fleck LE, LaFleur MD, Isabella VM et al. 2013. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature 503:7476365–70
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-062917-012848
Loading
/content/journals/10.1146/annurev-biochem-062917-012848
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error