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The C-terminal domain of M. tuberculosis ECF sigma factor I (SigI) interferes in SigI-RNAP interaction

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Abstract

Mycobacterium tuberculosis is equipped with diversified ECF sigma factors that are generally expressed under adverse environmental conditions. Mtb-SigI belongs to the ECF41 family of sigma factor, and no information is available about their expression during stringent response. This study provides the structural insight of Mtb-SigI and the characterization of its C-terminal polypeptide extension. C-terminal site of Mtb-SigI is truncated in two ways: (a) conserved region of C-terminal extension is preserved while the rest of the portion is deleted and (b) complete deletion of C-terminal extension. Each of the wild-type and truncated Mtb-SigI is docked with a β subunit of core RNA polymerase and simulated for 100 ns. Relative binding strength calculated from trajectory analysis reflects that the complete deletion of the C-terminal extension of Mtb-SigI favors interaction with core RNA polymerase. It can be implicated that the C-terminal domain in the wild-type docked complex help flipping of domain 4 of Mtb-SigI and thereby impaired holoenzyme formation. When the C-terminal extension is partially deleted, such flipping of domain 4 of Mtb-SigI diminishes and complete deletion of C-terminal extension promotes holoenzyme formation. In the absence of any sigma factor antagonist, the C-terminal extension of Mtb-SigI might behave as a complex player in transcription regulation.

Graphical abstract

Role of Mtb-SigI in transcription regulation

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References

  1. WHO Global tuberculosis control. (2011) Available online at http://www.who.int/entity/tb/publications/global_report/2011/gtbr11_full.pdf. Accessed 24 Dec 2012

  2. Wirth T, Hildebrand F, Allix-Béguec C, Wolbeling F, Kubica T, Kremer K, van Soolingen D, Rüsch-Gerdes S, Locht C, Brisse S, Meyer A, Supply P, Niemann S (2008) Origin, spread and demography of the Mycobacterium tuberculosis complex. PLoS Pathog 4:e1000160

    Article  Google Scholar 

  3. Kaufmann SH (2002) Protection against tuberculosis: cytokines, T cells, and macrophages. Ann Rheum Dis 61:ii54–ii58

    Article  CAS  Google Scholar 

  4. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544

    Article  CAS  Google Scholar 

  5. Manganelli R, Provvedi R, Rodrigue S, Beaucher J, Gaudreau L, Smith I (2004) Sigma factors and global gene regulation in Mycobacterium tuberculosis. J Bacteriol 186:895–902

    Article  CAS  Google Scholar 

  6. Starón A, Sofia HJ, Dietrich S, Ulrich LE, Liesegang H, Mascher T (2009) The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) sigma factor protein family. Mol Microbiol 74:557–581

    Article  Google Scholar 

  7. Hu Y, Coates AR (2001) Increased levels of sigJ mRNA in late stationary phase cultures of Mycobacterium tuberculosis detected by DNA array hybridization. FEMS Microbiol Lett 202:59–65

    Article  CAS  Google Scholar 

  8. Hu Y, Kendall S, Stoker NG, Coates AR (2004) The Mycobacterium tuberculosis sigJ gene controls the sensitivity of the bacterium to hydrogen peroxide. FEMS Microbiol Lett 237:415–423

    CAS  PubMed  Google Scholar 

  9. Homerova D, Halgasova L, Kormanec J (2008) Cascade of extracytoplasmic function sigma factors in Mycobacterium tuberculosis: identification of a sigma J-dependent promoter upstream of sigI. FEMS Microbiol Lett 280:20–26

    Article  Google Scholar 

  10. Goutam K, Gupta AK, Gopal B (2017) The fused SnoaL_2 domain in the Mycobacterium tuberculosis sigma factor σJ modulates promoter recognition. Nucleic Acids Res 45:9760–9772

    Article  CAS  Google Scholar 

  11. Bairoch A, Apweiler R, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Natale DA, O’Donovan C, Redaschi N, Yeh LS (2005) The Universal Protein Resource (UniProt). Nucleic Acids Res 33(Database issue):D154–D159

    Article  CAS  Google Scholar 

  12. Bradley P, Misura KM, Baker D (2005) Toward high-resolution de novo structure prediction for small proteins. Science 309:1868–1871

    Article  CAS  Google Scholar 

  13. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447

    Article  CAS  Google Scholar 

  14. Oostenbrink C, Villa A, Mark AE, van Gunsteren WF (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 25:1656–1676

    Article  CAS  Google Scholar 

  15. Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1969) Interaction models for water in relation to protein hydration. Nature 224:175–177

    Article  Google Scholar 

  16. Darden D, York L (1993) Pedersen particle mesh Ewald: an N; log (N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  17. Sippl MJ (1993) Recognition of errors in three-dimensional structures of proteins. Proteins 17:355–362

    Article  CAS  Google Scholar 

  18. Wiederstein M, Sippl MJ (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 35(Web server issue):W407–W410

    Article  Google Scholar 

  19. Comeau SR, Gatchell DW, Vajda S, Camacho CJ (2004) ClusPro: a fully automated algorithm for protein-protein docking. Nucleic Acids Res 32(Web Server issue):W96–W99

    Article  CAS  Google Scholar 

  20. Comeau SR, Gatchell DW, Vajda S, Camacho CJ (2004) ClusPro: an automated docking and discrimination method for the prediction of protein complexes. Bioinfo 20:45–50

    Article  CAS  Google Scholar 

  21. Kozakov D, Brenke R, Comeau SR, Vajda S (2006) PIPER: an FFT-based protein docking program with pairwise potentials. Proteins 65:392–406

    Article  CAS  Google Scholar 

  22. Kozakov D, Beglov D, Bohnuud T, Mottarella SE, Xia B, Hall DR, Vajda S (2013) How good is automated protein docking? Proteins 81:2159–2166

    Article  CAS  Google Scholar 

  23. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(33–8):27–28

    Google Scholar 

  24. Oostenbrink C, Villa A, Mark AE, van Gunsteren WF (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. Comput Chem 13:1656–1676

    Article  Google Scholar 

  25. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N; log (N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  26. Gupta AM, Pal P, Mandal S (2016) Structural analysis of sigma E interactions with core RNA polymerase and its cognate P-hsp20 promoter of Mycobacterium tuberculosis. J Biomol Struct Dyn 34:792–799

    Article  CAS  Google Scholar 

  27. Geszvain K, Gruber TM, Mooney RA, Gross CA, Landick RJ (2004) A hydrophobic patch on the flap-tip helix of E. coli RNA polymerase mediates sigma(70) region 4 function. J Mol Biol 343:569–587

    Article  CAS  Google Scholar 

  28. Wecke T, Halang P, Staro’n A, Dufour YS, Donohue TJ, Mascher T (2012) Extracytoplasmic function sigma factors of the widely distributed group ECF41 contain a fused regulatory domain. Microbiol Open 1:194–213

    Article  CAS  Google Scholar 

  29. Lin W, Mandal S, Degen D, Cho MS, Feng Y, Das K, Ebright RH (2019) Structural basis of ECF-σ-factor-dependent transcription initiation. Nat Commun 10:710

    Article  CAS  Google Scholar 

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Acknowledgments

Fellowship of AMG and part of the research is supported by grant no 548 (Sanc)/ST/P/S&T/9G-5/2015 funded by Department of Science &Technology, Govt. of West Bengal, India. Authors are grateful to the High-Performance Computing for Modern Biology (CHPC lab), University of Calcutta, for providing the infrastructure to do the work. Simulations are conducted utilizing Bioinformatics Resources and Applications Facility (BRAF), C-DAC, Pune.

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  1. Laboratory of Molecular Bacteriology, Department of Microbiology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India

    Aayatti Mallick Gupta & Sukhendu Mandal

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  1. Aayatti Mallick Gupta
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  2. Sukhendu Mandal
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Correspondence to Sukhendu Mandal.

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Mallick Gupta, A., Mandal, S. The C-terminal domain of M. tuberculosis ECF sigma factor I (SigI) interferes in SigI-RNAP interaction. J Mol Model 26, 77 (2020). https://doi.org/10.1007/s00894-020-4322-y

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