Advertisement

Current Genetics

, Volume 65, Issue 2, pp 363–370 | Cite as

Structural modules of the stress-induced protein HflX: an outlook on its evolution and biological role

  • Krishnamoorthi Srinivasan
  • Sandip Dey
  • Jayati SenguptaEmail author
Review
  • 124 Downloads

Abstract

Multifunctional proteins often show modular structures. A functional domain and the structural modules within the domain show evolutionary conservation of their spatial arrangement since that gives the protein its functionality. However, the question remains as to how members of different domains of life (Archaea, Bacteria, Eukarya), polish and perfect these modules within conserved multidomain proteins, to tailor functional proteins according to their specific requirements. In the quest for plausible answers to this question, we studied the bacterial protein HflX. HflX is a universally conserved member of the Obg-GTPase superfamily but its functional role in Archaea and Eukarya is barely known. It is a multidomain protein and possesses, in addition to its conserved GTPase domain, an ATP-binding N-terminal domain. It is involved in heat stress response in Escherichia coli and our laboratory recently identified an ATP-dependent RNA helicase activity of E. coli HflX, which is likely instrumental in rescuing ribosomes during heat stress. Because perception and response to stress is expected to be different in different life forms, the question is whether this activity is preserved in higher organisms or not. Thus, we explored the evolution pattern of different structural modules of HflX, with particular emphasis on the ATP-binding domain, to understand plausible biological role of HflX in other forms of life. Our analyses indicate that, while the evolutionary pattern of the GTPase domain follows a conserved phylogeny, conservation of the ATP-binding domain shows a complicated pattern. The limited analysis described here hints towards possible evolutionary adaptations and modifications of the domain, something which needs to be investigated in more depth in homologs from other life forms. Deciphering how nature ‘tweaks’ such modules, both structurally and functionally, may help in understanding the evolution of such proteins, and, on a large-scale, of stress-related proteins in general as well.

Keywords

Universally conserved proteins Structural modules Stress response ATPase activity Evolution 

Notes

Acknowledgements

This work was supported by CSIR Network project ‘UNSEEN’ (BSC0113), SERB (SB/SO/BB-0025/2014) (DST, India) sponsored project, and CSIR-Indian Institute of Chemical Biology, Kolkata, India. KS and SD acknowledge fellowships awarded by CSIR and UGC, India, respectively. We sincerely thank Dr. Zoran Ilic of Wadsworth Center, Albany, NY, USA, for valuable suggestions on the manuscript.

References

  1. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402CrossRefGoogle Scholar
  2. Ash MR, Maher MJ, Mitchell Guss J, Jormakka M (2012) The cation-dependent G-proteins: in a class of their own. FEBS Lett 586:2218–2224.  https://doi.org/10.1016/j.febslet.2012.06.030 CrossRefGoogle Scholar
  3. Baker CR, Booth LN, Sorrells TR, Johnson AD (2012) Protein modularity, cooperative binding, and hybrid regulatory states underlie transcriptional network diversification. Cell 151:80–95.  https://doi.org/10.1016/j.cell.2012.08.018 CrossRefGoogle Scholar
  4. Carruthers MD, Minion C (2009) Transcriptome analysis of Escherichia coli O157:H7 EDL933 during heat shock. FEMS Microbiol Lett.  https://doi.org/10.1111/j.1574-6968.2009.01587.x Google Scholar
  5. Chuang SE, Blattner FR (1993) Characterization of twenty-six new heat shock genes of Escherichia coli. J Bacteriol.  https://doi.org/10.1128/jb.175.16.5242-5252.1993 Google Scholar
  6. Coatham ML, Brandon HE, Fischer JJ, Schummer T, Wieden HJ (2016) The conserved GTPase HflX is a ribosome splitting factor that binds to the E-site of the bacterial ribosome. Nucleic Acids Res 44:1952–1961 p doCrossRefGoogle Scholar
  7. Corpet F (1988) Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res 16:10881–10890 doiCrossRefGoogle Scholar
  8. Defenouillere Q, Fromont-Racine M (2017) The ribosome-bound quality control complex: from aberrant peptide clearance to proteostasis maintenance. Curr Genet 63:997–1005.  https://doi.org/10.1007/s00294-017-0708-5 CrossRefGoogle Scholar
  9. Dey S, Biswas C, Sengupta J (2018) The universally conserved GTPase HflX is an RNA helicase that restores heat-damaged Escherichia coli ribosomes. J cell Biol 217:2519–2529.  https://doi.org/10.1083/jcb.201711131 CrossRefGoogle Scholar
  10. Dutta D, Bandyopadhyay K, Datta AB, Sardesai AA, Parrack P (2009) Properties of HflX, an enigmatic protein from Escherichia coli. J Bacteriol.  https://doi.org/10.1128/JB.01353-08 Google Scholar
  11. Fischer JJ, Coatham ML, Eagle Bear S, Brandon HE, De Laurentiis EI, Shields MJ, Wieden HJ (2012) The ribosome modulates the structural dynamics of the conserved GTPase HflX and triggers tight nucleotide binding. Biochimie.  https://doi.org/10.1016/j.biochi.2012.04.016 Google Scholar
  12. Gô M, Nosaka M, Tomoda S (1993) Domains and modules of proteins. In: Imahori KSF (ed) Methods in protein sequence analysis. Springer, BostonGoogle Scholar
  13. Gō M (1985) Protein structures and split genes. Adv Biophys 19:91–131CrossRefGoogle Scholar
  14. Gohara DW, Yap MF (2018) Survival of the drowsiest: the hibernating 100S ribosome in bacterial stress management. Curr Genet 64:753–760.  https://doi.org/10.1007/s00294-017-0796-2 CrossRefGoogle Scholar
  15. Gorrell A, Lawrence SH, Ferry JG (2005) Structural and kinetic analyses of arginine residues in the active site of the acetate kinase from Methanosarcina thermophila. J Biol Chem 280:10731–10742.  https://doi.org/10.1074/jbc.M412118200 CrossRefGoogle Scholar
  16. Inbar D, Hochman J, Givol D (1972) Localization of antibody-combining sites within the variable portions of heavy and light chains. Proc Natl Acad Sci USA.  https://doi.org/10.1073/pnas.69.9.2659 Google Scholar
  17. Jain N, Dhimole N, Khan AR, De D, Tomar SK, Sajish M, Dutta D, Parrack P, Prakash B (2009) E. coli HflX interacts with 50S ribosomal subunits in presence of nucleotides. Biochem Biophys Res Commun.  https://doi.org/10.1016/j.bbrc.2008.12.072 Google Scholar
  18. Jain N, Vithani N, Rafay A, Prakash B (2013) Identification and characterization of a hitherto unknown nucleotide-binding domain and an intricate interdomain regulation in HflX-a ribosome binding GTPase. Nucleic Acids Res 41:9557–9569 p doCrossRefGoogle Scholar
  19. Jiang LH, Rassendren F, Surprenant A, North RA (2000) Identification of amino acid residues contributing to the ATP-binding site of a purinergic P2X receptor. J Biol Chem 275:34190–34196.  https://doi.org/10.1074/jbc.M005481200 CrossRefGoogle Scholar
  20. Kaur G, Sengupta S, Kumar V, Kumari A, Ghosh A, Parrack P, Dutta D (2014) Novel MntR-Independent mechanism of manganese homeostasis in escherichia coli by the ribosome-associated protein HflX. J Bacteriol.  https://doi.org/10.1128/JB.01717-14 Google Scholar
  21. Khan T, Ghosh I (2015) Modularity in protein structures: study on all-alpha proteins. J Biomol Struct Dyn.  https://doi.org/10.1080/07391102.2014.1003969 Google Scholar
  22. Leipe DD, Wolf YI, Koonin EV, Aravind L (2002) Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol 317:41–72.  https://doi.org/10.1006/jmbi.2001.5378 CrossRefGoogle Scholar
  23. Matzov D, Aibara S, Basu A, Zimmerman E, Bashan A, Yap MF, Amunts A, Yonath AE (2017) The cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococcus aureus. Nature Commun 8:723.  https://doi.org/10.1038/s41467-017-00753-8 CrossRefGoogle Scholar
  24. Melnikov S, Ben-Shem A, Garreau de Loubresse N, Jenner L, Yusupova G, Yusupov M (2012) One core, two shells: bacterial and eukaryotic ribosomes. Nat Struct Mol Biol 19:560–567.  https://doi.org/10.1038/nsmb.2313 CrossRefGoogle Scholar
  25. Moore AD, Bjorklund AK, Ekman D, Bornberg-Bauer E, Elofsson A (2008) Arrangements in the modular evolution of proteins. Trends Biochem Sci 33:444–451.  https://doi.org/10.1016/j.tibs.2008.05.008 CrossRefGoogle Scholar
  26. Myasnikov AG, Simonetti A, Marzi S, Klaholz BP (2009) Structure-function insights into prokaryotic and eukaryotic translation initiation. Curr Opin Struct Biol 19:300–309.  https://doi.org/10.1016/j.sbi.2009.04.010 CrossRefGoogle Scholar
  27. Nerurkar P, Altvater M, Gerhardy S, Schutz S, Fischer U, Weirich C, Panse VG (2015) Eukaryotic ribosome assembly and nuclear export. Int Rev Cell Mol Biol 319:107–140.  https://doi.org/10.1016/bs.ircmb.2015.07.002 CrossRefGoogle Scholar
  28. Noble JA, Innis MA, Koonin EV, Rudd KE, Banuett F, Herskowitz I (1993) The Escherichia coli hflA locus encodes a putative GTP-binding protein and two membrane proteins, one of which contains a protease-like domain. Proc Natl Acad Sci USA.  https://doi.org/10.1073/pnas.90.22.10866 Google Scholar
  29. Pauling L (1940) A theory of the structure and process of formation of antibodies. J Am Chem Soc.  https://doi.org/10.1021/ja01867a018 Google Scholar
  30. Ramakrishnan V (2002) Ribosome structure and the mechanism of translation. Cell 108:557–572 p doCrossRefGoogle Scholar
  31. Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40:253–266.  https://doi.org/10.1016/j.molcel.2010.10.006 CrossRefGoogle Scholar
  32. Schrijen JJ, Luyben WA, De Pont JJ, Bonting SL (1980) Studies on (K + + H+)-ATPase. I. Essential arginine residue in its substrate binding center. Biochim Biophys Acta 597:331–344 doiCrossRefGoogle Scholar
  33. Siltberg-Liberles J, Grahnen JA, Liberles DA (2011) The evolution of protein structures and structural ensembles under functional constraint. Genes 2:748–762.  https://doi.org/10.3390/genes2040748 CrossRefGoogle Scholar
  34. Sloan KE, Warda AS, Sharma S, Entian KD, Lafontaine DLJ, Bohnsack MT (2017) Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function. RNA Biol 14:1138–1152.  https://doi.org/10.1080/15476286.2016.1259781 CrossRefGoogle Scholar
  35. Spitaler M, Villunger A, Grunicke H, Uberall F (2000) Unique structural and functional properties of the ATP-binding domain of atypical protein kinase C-iota. J Biol Chem 275:33289–33296.  https://doi.org/10.1074/jbc.M002742200 CrossRefGoogle Scholar
  36. Thompson JD, Gibson TJ, Higgins DG (2002) Multiple sequence alignment using ClustalW and ClustalX. Curr Protocols Bioinf 1:2–3Google Scholar
  37. Trifonov EN, Frenkel ZM (2009) Evolution of protein modularity. Curr Opin Struct Biol 19:335–340.  https://doi.org/10.1016/j.sbi.2009.03.007 CrossRefGoogle Scholar
  38. Trott O, Olson AJ (2010) AutoDock Vina. J Comput Chem.  https://doi.org/10.1002/jcc.21334 Google Scholar
  39. Tsui HCT, Feng G, Winkler ME (1996) Transcription of the mutL repair, miaA tRNA modification, hfq pleiotropic regulator, and hflA region protease genes of Escherichia coli K-12 from clustered Eσ32-specific promoters during heat shock. J Bacteriol 178:5719–5731CrossRefGoogle Scholar
  40. Verstraeten N, Fauvart M, Versees W, Michiels J (2011) The universally conserved prokaryotic GTPases. Microbiol Mol Biol Rev 75:507–542.  https://doi.org/10.1128/MMBR.00009-11 (second and third pages of table of contents)CrossRefGoogle Scholar
  41. Weinmaster G, Zoller MJ, Pawson T (1986) A lysine in the ATP-binding site of P130gag-fps is essential for protein-tyrosine kinase activity. EMBO J 5:69–76 doiCrossRefGoogle Scholar
  42. Wu H, Sun L, Blombach F, Brouns SJ, Snijders AP, Lorenzen K, van den Heuvel RH, Heck AJ, Fu S, Li X, Zhang XC, Rao Z, van der Oost J (2010) Structure of the ribosome associating GTPase HflX. Proteins 78:705–713.  https://doi.org/10.1002/prot.22599 CrossRefGoogle Scholar
  43. Yusupova G, Yusupov M (2014) High-resolution structure of the eukaryotic 80S ribosome. Annu Rev Biochem 83:467–486.  https://doi.org/10.1146/annurev-biochem-060713-035445 CrossRefGoogle Scholar
  44. Yutin N, Puigbò P, Koonin EV, Wolf YI (2012) Phylogenomics of prokaryotic ribosomal proteins. PLoS One.  https://doi.org/10.1371/journal.pone.0036972 Google Scholar
  45. Zhang Y, Mandava CS, Cao W, Li X, Zhang D, Li N, Zhang Y, Zhang X, Qin Y, Mi K, Lei J, Sanyal S, Gao N (2015) HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions. Nature Struct Mol Biol.  https://doi.org/10.1038/nsmb.3103 Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Structural Biology and Bio-Informatics DivisionCSIR-Indian Institute of Chemical BiologyKolkataIndia

Personalised recommendations