Post-Translational Regulation via Clp Protease Is Critical for Survival of

English version České info

To date, studies on the regulation of physiology and virulence in Mycobacterium tuberculosis (Mtb) have focused on how transcriptional changes lead to adaptation. Interestingly, Mtb has numerous proteases that are essential for normal growth suggesting that protein turnover may also play an important regulatory role in the pathogen. We used novel methods to identify the set of proteins that are degraded by the essential Clp protease. The degradation of one protein, WhiB1, was required for normal growth confirming that inhibiting turnover of certain substrates can have a lethal effect. The understanding of essential pathways in Mtb will be important for the discovery of novel drugs to aid in the global fight against tuberculosis.

Vyšlo v časopise: Post-Translational Regulation via Clp Protease Is Critical for Survival of. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003994
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003994

Souhrn

Zdroje

1. GlickmanMH, CiechanoverA (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82: 373–428 doi:10.1152/physrev.00027.2001

2. GoldbergAL (2007) Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy. Biochem Soc Trans 35: 12–17 doi:10.1042/BST0350012

3. BakerTA, SauerRT (2006) ATP-dependent proteases of bacteria: recognition logic and operating principles. Trends Biochem Sci 31: 647–653 doi:10.1016/j.tibs.2006.10.006

4. PallenMJ, WrenBW (1997) The HtrA family of serine proteases. Molecular Microbiology 26: 209–221.

5. GerthU, KockH, KustersI, MichalikS, SwitzerRL, et al. (2008) Clp-dependent proteolysis down-regulates central metabolic pathways in glucose-starved Bacillus subtilis. J Bacteriol 190: 321–331 doi:10.1128/JB.01233-07

6. HongS-J, LessnerFH, MahenEM, KeilerKC (2007) Proteomic identification of tmRNA substrates. Proc Natl Acad Sci USA 104: 17128–17133 doi:10.1073/pnas.0707671104

7. World Health Organization (2011) Global tuberculosis control: WHO report 2011. Geneva, Switzerland: World Health Organization.

8. DamerauK, St JohnAC (1993) Role of Clp protease subunits in degradation of carbon starvation proteins in Escherichia coli. J Bacteriol 175: 53–63.

9. GerthU, KrugerE, DerréI, MsadekT, HeckerM (1998) Stress induction of the Bacillus subtilis clpP gene encoding a homologue of the proteolytic component of the Clp protease and the involvement of ClpP and ClpX in stress tolerance. Molecular Microbiology 28: 787–802.

10. SassettiCM, BoydDH, RubinEJ (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Molecular Microbiology 48: 77–84.

11. RajuRM, UnnikrishnanM, RubinDHF, KrishnamoorthyV, KandrorO, et al. (2012) Mycobacterium tuberculosis ClpP1 and ClpP2 Function Together in Protein Degradation and Are Required for Viability in vitro and During Infection. PLoS Pathog 8: e1002511 doi:10.1371/journal.ppat.1002511.g005

12. CarrollP, Faray-KeleM-C, ParishT (2011) Identifying vulnerable pathways in Mycobacterium tuberculosis using a knock-down approach. Applied and Environmental Microbiology 77: 1–19 doi:10.1128/AEM.02880-10

13. AkopianT, KandrorO, RajuRM, UnnikrishnanM, RubinEJ, et al. (2012) The active ClpP protease from M. tuberculosis is a complex composed of a heptameric ClpP1 and a ClpP2 ring. EMBO J 31: 1–13 doi:10.1038/emboj.2012.5

14. NeuwaldAF, AravindL, SpougeJL, KooninEV (1999) AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9: 27–43.

15. Ribeiro-GuimarãesML, PessolaniMCV (2007) Comparative genomics of mycobacterial proteases. Microb Pathog 43: 173–178 doi:10.1016/j.micpath.2007.05.010

16. KimJ-H, WeiJ-R, WallachJB, RobbinsRS, RubinEJ, et al. (2010) Protein inactivation in mycobacteria by controlled proteolysis and its application to deplete the beta subunit of RNA polymerase. Nucleic Acids Res 39(6): 2210–20 doi:10.1093/nar/gkq1149

17. DayonL, HainardA, LickerV, TurckN, KuhnK, et al. (2008) Relative Quantification of Proteins in Human Cerebrospinal Fluids by MS/MS Using 6-Plex Isobaric Tags. Anal Chem 80: 2921–2931 doi:10.1021/ac702422x

18. TingL, RadR, GygiSP, HaasW (2011) MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics. Nat Methods 8: 937–940 doi:10.1038/nmeth.1714

19. SaeedAI, BhagabatiNK, BraistedJC, LiangW, SharovV, et al. (2006) TM4 microarray software suite. Meth Enzymol 411: 134–193 doi:10.1016/S0076-6879(06)11009-5

20. AshburnerM, BallCA, BlakeJA, BotsteinD, ButlerH, et al. (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25: 25–29 doi:10.1038/75556

21. SmithLJ, StapletonMR, FullstoneGJM, CrackJC, ThomsonAJ, et al. (2010) Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster. Biochem J 432: 417–427 doi:10.1042/BJ20101440

22. FlynnJM, NeherSB, KimYI, SauerRT, BakerTA (2003) Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol Cell 11: 671–683.

23. FengJ, MichalikS, VarmingAN, AndersenJH, AlbrechtD, et al. (2013) Trapping and Proteomic Identification of Cellular Substrates of the ClpP Protease in Staphylococcus aureus. J Proteome Res 12: 547–558 doi:10.1021/pr300394r

24. TobiasJW, ShraderTE, RocapG, VarshavskyA (1991) The N-end rule in bacteria. Science 254: 1374–1377.

25. JenalU, FuchsT (1998) An essential protease involved in bacterial cell-cycle control. EMBO J 17: 5658–5669 doi:10.1093/emboj/17.19.5658

26. SinghA, GuidryL, NarasimhuluKV, MaiD, TrombleyJ, et al. (2007) Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival. Proc Natl Acad Sci USA 104: 11562–11567 doi:10.1073/pnas.0700490104

27. GargSK, Suhail AlamM, SoniV, Radha KishanKV, AgrawalP (2007) Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase. Protein Expression and Purification 52: 422–432 doi:10.1016/j.pep.2006.10.015

28. SteynAJC, CollinsDM, HondalusMK, JacobsWR, KawakamiRP, et al. (2002) Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci USA 99: 3147–3152 doi:10.1073/pnas.052705399

29. ReddyTBK, RileyR, WymoreF, MontgomeryP, DeCaprioD, et al. (2009) TB database: an integrated platform for tuberculosis research. Nucleic Acids Res 37: D499–D508 doi:10.1093/nar/gkn652

30. GottesmanS, RocheE, ZhouY, SauerRT (1998) The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. Genes Dev 12: 1338–1347.

31. ZhangYJ, IoergerTR, HuttenhowerC, LongJE, SassettiCM, et al. (2012) Global Assessment of Genomic Regions Required for Growth in Mycobacterium tuberculosis. PLoS Pathog 8: e1002946 doi:10.1371/journal.ppat.1002946.g005

32. ShiW, ZhangX, JiangX, YuanH, LeeJS, et al. (2011) Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 333: 1630–1632 doi:10.1126/science.1208813

33. StallingsCL, StephanouNC, ChuL, HochschildA, NickelsBE, et al. (2009) CarD Is an Essential Regulator of rRNA Transcription Required for Mycobacterium tuberculosis Persistence. Cell 138: 146–159 doi:10.1016/j.cell.2009.04.041