Skip to main content
SpringerLink
Log in

A Unified Catalytic Mechanism for Cyclic di-NMP Hydrolysis by DHH–DHHA1 Phosphodiesterases

  • Chapter
  • First Online:
Microbial Cyclic Di-Nucleotide Signaling

Abstract

Cyclic di-AMP is a vital second messenger other than cyclic di-GMP that regulates diverse cellular physiological processes in many bacteria. Its cellular level is controlled by the counter-actions of diadenylate cyclases (DAC) and phosphodiesterases (PDE). Three kinds of PDEs have been identified to date that contain either a DHH–DHHA1 domain, an HD domain, or a metallo-phosphoesterase domain, respectively. The DHH–DHHA1 PDEs are of special interest because of their functional diversity. They can be further subdivided into either membrane-bound GdpP or stand-alone Rv2837c phosphodiesterase, which degrade cyclic di-AMP into linear 5′-pApA and AMP, respectively. The DHH–DHHA1 PDEs can also hydrolyze other cyclic di-NMPs (cyclic di-GMP or cGAMP) with low activity. In this chapter, we review the structures and functions of the DHH–DHHA1 domain of GdpP and Rv2837c that we reported in recent years. According to detailed structural and enzymatic analyses, we have summarized a unified molecular mechanism for the DHH–DHHA1 PDEs and systematically analyzed the catalytic activities of DHH–DHHA1 PDEs on other cyclic di-NMPs (cyclic di-GMP and cGAMP).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cotter PA, Stibitz S (2007) c-di-GMP-mediated regulation of virulence and biofilm formation. Curr Opin Microbiol 10(1):17–23. https://doi.org/10.1016/j.mib.2006.12.006

    Article  CAS  PubMed  Google Scholar 

  2. Krasteva PV, Fong JC, Shikuma NJ, Beyhan S, Navarro MV, Yildiz FH, Sondermann H (2010) Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP. Science 327(5967):866–868. https://doi.org/10.1126/science.1181185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Witte G, Hartung S, Buttner K, Hopfner KP (2008) Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Mol Cell 30(2):167–178. https://doi.org/10.1016/j.molcel.2008.02.020

    Article  CAS  PubMed  Google Scholar 

  4. Corrigan RM, Grundling A (2013) Cyclic di-AMP: another second messenger enters the fray. Nat Rev Microbiol 11(8):513–524. https://doi.org/10.1038/nrmicro3069

    Article  CAS  PubMed  Google Scholar 

  5. Commichau FM, Dickmanns A, Gundlach J, Ficner R, Stulke J (2015) A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP. Mol Microbiol 97(2):189–204. https://doi.org/10.1111/mmi.13026

    Article  CAS  PubMed  Google Scholar 

  6. Davies BW, Bogard RW, Young TS, Mekalanos JJ (2012) Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell 149(2):358–370. https://doi.org/10.1016/j.cell.2012.01.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nelson JW, Sudarsan N, Phillips GE, Stav S, Lunse CE, McCown PJ, Breaker RR (2015) Control of bacterial exoelectrogenesis by c-AMP-GMP. Proc Natl Acad Sci USA 112(17):5389–5394. https://doi.org/10.1073/pnas.1419264112

    Article  CAS  PubMed  Google Scholar 

  8. Sun LJ, Wu JX, Du FH, Chen X, Chen ZJJ (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121):786–791. https://doi.org/10.1126/science.1232458

    Article  CAS  PubMed  Google Scholar 

  9. Kranzusch PJ, Wilson SC, Lee AS, Berger JM, Doudna JA, Vance RE (2015) Ancient origin of cGAS-STING reveals mechanism of universal 2′,3′ cGAMP signaling. Mol Cell 59(6):891–903. https://doi.org/10.1016/j.molcel.2015.07.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xiao TS, Fitzgerald KA (2013) The cGAS-STING pathway for DNA sensing. Mol Cell 51(2):135–139. https://doi.org/10.1016/j.molcel.2013.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Margolis SR, Wilson SC, Vance RE (2017) Evolutionary origins of cGAS-STING signaling. Trends Immunol 38(10):733–743. https://doi.org/10.1016/j.it.2017.03.004

    Article  CAS  PubMed  Google Scholar 

  12. Jenal U, Reinders A, Lori C (2017) Cyclic di-GMP: second messenger extraordinaire. Nat Rev Microbiol 15(5):271–284. https://doi.org/10.1038/nrmicro.2016.190

    Article  CAS  PubMed  Google Scholar 

  13. Huynh TN, Luo S, Pensinger D, Sauer JD, Tong L, Woodward JJ (2015) An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence. Proc Natl Acad Sci USA 112(7):E747–E756. https://doi.org/10.1073/pnas.1416485112

    Article  CAS  PubMed  Google Scholar 

  14. Andrade WA, Firon A, Schmidt T, Hornung V, Fitzgerald KA, Kurt-Jones EA, Trieu-Cuot P, Golenbock DT, Kaminski PA (2016) Group B streptococcus degrades cyclic-di-AMP to modulate STING-dependent type I interferon production. Cell Host Microbe 20(1):49–59. https://doi.org/10.1016/j.chom.2016.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. He Q, Wang F, Liu SH, Zhu DY, Cong HJ, Gao F, Li BQ, Wang HW, Lin Z, Liao J, Gu LC (2016) Structural and biochemical insight into the mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP phosphodiesterase (vol 291, pg 3668, 2016). J Biol Chem 291(27):14386–14387. https://doi.org/10.1074/jbc.A115.699801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao A, Serganov A (2014) Structural insights into recognition of c-di-AMP by the ydaO riboswitch. Nat Chem Biol 10(9):787–792. https://doi.org/10.1038/Nchembio.1607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sureka K, Choi PH, Precit M, Delince M, Pensinger DA, Huynh TN, Jurado AR, Goo YA, Sadilek M, Iavarone AT, Sauer JD, Tong L, Woodward JJ (2014) The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function. Cell 158(6):1389–1401. https://doi.org/10.1016/j.cell.2014.07.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Aravind L, Koonin EV (1998) A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial RecJ exonuclease. Trends Biochem Sci 23(1):17–19

    Article  CAS  Google Scholar 

  19. Makarova KS, Koonin EV, Kelman Z (2012) The CMG (CDC45/RecJ, MCM, GINS) complex is a conserved component of the DNA replication system in all archaea and eukaryotes. Biol Direct 7:7. https://doi.org/10.1186/1745-6150-7-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Feng L, Chang CC, Song D, Jiang C, Song Y, Wang CF, Deng W, Zou YJ, Chen HF, Xiao X, Wang FP, Liu XP (2018) The trimeric Hef-associated nuclease HAN is a 3′→5′ exonuclease and is probably involved in DNA repair. Nucleic Acids Res 46(17):9027–9043. https://doi.org/10.1093/nar/gky707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rao F, See RY, Zhang DW, Toh DC, Ji Q, Liang ZX (2010) YybT is a signaling protein that contains a cyclic dinucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity. J Biol Chem 285(1):473–482. https://doi.org/10.1074/jbc.M109.040238

    Article  CAS  PubMed  Google Scholar 

  22. Bai Y, Yang J, Eisele LE, Underwood AJ, Koestler BJ, Waters CM, Metzger DW, Bai G (2013) Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP phosphodiesterase activity and affect bacterial growth and virulence. J Bacteriol 195(22):5123–5132. https://doi.org/10.1128/JB.00769-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Corrigan RM, Abbott JC, Burhenne H, Kaever V, Grundling A (2011) c-di-AMP is a new second messenger in Staphylococcus aureus with a role in controlling cell size and envelope stress. PLoS Pathog 7(9):e1002217. https://doi.org/10.1371/journal.ppat.1002217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huynh TN, Woodward JJ (2016) Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm. Curr Opin Microbiol 30:22–29. https://doi.org/10.1016/j.mib.2015.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang F, He Q, Su KX, Wei TD, Xu SJ, Gu LC (2018) Structural and biochemical characterization of the catalytic domains of GdpP reveals a unified hydrolysis mechanism for the DHH/DHHA1 phosphodiesterase. Biochem J 475:191–205. https://doi.org/10.1042/Bcj20170739

    Article  CAS  PubMed  Google Scholar 

  26. Postic G, Danchin A, Mechold U (2012) Characterization of NrnA homologs from Mycobacterium tuberculosis and Mycoplasma pneumoniae. RNA 18(1):155–165. https://doi.org/10.1261/rna.029132.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Srivastav R, Kumar D, Grover A, Singh A, Manjasetty BA, Sharma R, Taneja B (2014) Unique subunit packing in mycobacterial nanoRNase leads to alternate substrate recognitions in DHH phosphodiesterases. Nucleic Acids Res 42(12):7894–7910. https://doi.org/10.1093/nar/gku425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yang J, Bai Y, Zhang Y, Gabrielle VD, Jin L, Bai G (2014) Deletion of the cyclic di-AMP phosphodiesterase gene (cnpB) in Mycobacterium tuberculosis leads to reduced virulence in a mouse model of infection. Mol Microbiol 93(1):65–79. https://doi.org/10.1111/mmi.12641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Drexler DJ, Muller M, Rojas-Cordova CA, Bandera AM, Witte G (2017) Structural and biophysical analysis of the soluble DHH/DHHA1-type phosphodiesterase TM1595 from Thermotoga maritima. Structure 25(12):1887–1897. https://doi.org/10.1016/j.str.2017.10.001

    Article  CAS  PubMed  Google Scholar 

  30. Uemura Y, Nakagawa N, Wakamatsu T, Kim K, Montelione GT, Hunt JF, Kuramitsu S, Masui R (2013) Crystal structure of the ligand-binding form of nanoRNase from Bacteroides fragilis, a member of the DHH/DHHA1 phosphoesterase family of proteins. FEBS Lett 587(16):2669–2674. https://doi.org/10.1016/j.febslet.2013.06.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Microbial Technology, Shandong University, Qingdao, People’s Republic of China

    Lichuan Gu & Qing He

Authors
  1. Lichuan Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lichuan Gu .

Editor information

Editors and Affiliations

  1. Institute of Biochemistry and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

    Shan-Ho Chou

  2. Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile

    Nicolas Guiliani

  3. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA

    Vincent T. Lee

  4. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Ute Römling

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gu, L., He, Q. (2020). A Unified Catalytic Mechanism for Cyclic di-NMP Hydrolysis by DHH–DHHA1 Phosphodiesterases. In: Chou, SH., Guiliani, N., Lee, V., Römling, U. (eds) Microbial Cyclic Di-Nucleotide Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-33308-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation