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Cytotoxic Potential of Novel Bacillary Ribonucleases Balnase and Balifase

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Abstract

In this work, a comparative analysis of structural organization and biological activity of low-molecular weight ribonucleases (RNases) secreted by Bacillus altitudinis (balnase) and B. licheniformis (balifase) with Bacillus pumilus RNase binase was performed. All three RNases are close homologs; however, binase and balnase differ by only one amino acid residue: polar uncharged threonine at position 106 in the binase molecule is replaced by a non-polar hydrophobic alanine in balnase. RNases share similar physicochemical properties (MW, pI, aliphatic index) but differ in stability of three-dimensional structures that reflects in their ability to inhibit proliferation of cancer cells. Binase forms more stable dimers as compared with balnase and balifase due to the swapping interactions between its molecules that possibly leads to a prolonged antiproliferative effect towards human lung adenocarcinoma A549 cells. The impact of oligomerization in biological effects of RNases is discussed.

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References

  1. Arraiano, C. M., Andrade, J. M., Domingues, S., Guinote, I. B., Malecki, M., Matos, R. G., Moreira, R. N., Pobre, V., Reis, F. P., Saramago, M., Silva, I. J., & Viegas, S. C. (2010). The critical role of RNA processing and degradation in the control of gene expression. FEMS Microbiology Reviews, 34, 883–923. https://doi.org/10.1111/j.1574-6976.2010.00242.x.

    Article  Google Scholar 

  2. Takahashi, K., & Moore, S. (1982). The enzymes. Nucleic acids (part B) (pp. 435–467). New York: Academic press.

    Book  Google Scholar 

  3. Chakrabarti, A., Jha, B. K., & Silverman, R. H. (2011). New insights into the role of RNase L in innate immunity. Journal of Interferon & Cytokine Research, 31, 49–57. https://doi.org/10.1089/jir.2010.0120.

    Article  Google Scholar 

  4. Rosenberg, H. F. (2008). RNase A ribonucleases and host defense: an evolving story. Journal of Leukocyte Biology, 83, 1079–1087. https://doi.org/10.1189/jlb.1107725.

    Article  Google Scholar 

  5. Gotte, G., Mahmoud Helmy, A., Ercole, C., Spadaccini, R., Laurents, D. V., Donadelli, M., & Picone, D. (2012). Double domain swapping in bovine seminal RNase: formation of distinct N- and C-swapped tetramers and multimers with increasing biological activities. PLoS One. https://doi.org/10.1371/journal.pone.0046804.

  6. Ilinskaya, O., Decker, K., Koschinski, A., Dreyer, F., & Repp, H. (2001). Bacillus intermedius ribonuclease as inhibitor of cell proliferation and membrane current. Toxicology, 156, 101–107. https://doi.org/10.1016/s0300-483x(00)00335-8.

    Article  Google Scholar 

  7. Mitkevich, V. A., Petrushanko, I. Y., Spirin, P. V., Fedorova, T. V., Kretova, O. V., Tchurikov, N. A., Prassol, V. S., Ilinskaya, O. N., & Makarov, A. A. (2011). Sensitivity of acute myeloid leukemia Kasumi-1 cells to binase toxic action depends on the expression of KIT and AML1-ETO oncogenes. Cell Cycle, 10, 4090–4097. https://doi.org/10.4161/cc.10.23.18210.

    Article  Google Scholar 

  8. Mitkevich, V. A., Schulga, A. A., Trofimov, A. A., Dorovatovskii, P. V., & Goncharuk, D. A. (2013). Structure and functional studies of the ribonuclease binase Glu43Ala/Phe81Ala mutant. Acta Crystallographica Section D, 69, 991–996. https://doi.org/10.1107/S0907444913004046.

    Article  Google Scholar 

  9. Dudkina, E., Kayumov, A., Ulyanova, V., & Ilinskaya, O. (2014). New insight into secreted ribonuclease structure: binase is a natural dimer. PLoS One. https://doi.org/10.1371/journal.pone.0115818.

  10. Zelenikhin, P. V., Makeeva, A. V., Nguen, T. N., Siraja, Y. A., & Ilinskaya, O. N. (2016). The combined action of binase and bleomycin on human lung adenocarcinoma cells. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 10, 87–90. https://doi.org/10.18097/PBMC20166203279.

    Article  Google Scholar 

  11. Liu, Y., Gotte, G., Libonati, M., & Eisenberg, D. (2001). A domain-swapped RNase A dimer with implications for amyloid formation. Nature Structural Biology, 8, 211–214. https://doi.org/10.1038/84941.

    Article  Google Scholar 

  12. Attery, A., Dey, P., Tripathi, P., & Batra, J. K. (2018). A ribonuclease inhibitor resistant dimer of human pancreatic ribonuclease displays specific antitumor activity. International Journal of Biological Macromolecules, 107, 1956–1970. https://doi.org/10.1016/j.ijbiomac.2017.10.067.

    Article  Google Scholar 

  13. Garvie, C. W., Vasanthavada, K., & Xiang, Q. (2013). Mechanistic insights into RNase L through use of an MDMX-derived multi-functional protein domain. Biochimica et Biophysica Acta, 1834, 1562–1571. https://doi.org/10.1016/j.bbapap.2013.04.010.

    Article  Google Scholar 

  14. Zuo, Y., & Deutscher, M. P. (2002). Mechanism of action of RNase T. II. A structural and functional model of the enzyme. The Journal of Biological Chemistry, 227, 50160–50164. https://doi.org/10.1074/jbc.M207707200.

    Article  Google Scholar 

  15. Poliakov, K. M., Goncharuk, D. A., Trofimov, A. A., Safonova, T. N., Mit’kevich, V. A., Tkach, E. N., Makarov, A. A., & Shulga, A. A. (2010). X-ray diffraction and biochemical studies of W34F mutant ribonuclease binase. Molecular Biology, 44, 922–928. https://doi.org/10.1134/S0026893310050195.

    Article  Google Scholar 

  16. Ilinskaya O, Ulyanova V, Lisevich I, Dudkina E, Zakharchenko N, Kusova A, Faizullin D, Zuev Yu (2018) The native monomer of Bacillus pumilus ribonuclease does not exist extracellularly. BioMed Research International 2018: 7p. doi: https://doi.org/10.1155/2018/4837623.

  17. Dudkina, E., Ulyanova, V., Shah Mahmud, R., Khodzhaeva, V., Dao, L., Vershinina, V., Kolpakov, A., & Ilinskaya, O. (2016). Three-step procedure for preparation of pure Bacillus altitudinis ribonuclease. FEBS Open Bio, 6, 24–32. https://doi.org/10.1002/2211-5463.12023.

    Article  Google Scholar 

  18. Sokurenko, Y., Nadyrova, A., Ulyanova, V., & Ilinskaya, O. (2016). Extracellular Ribonuclease from Bacillus licheniformis (Balifase), a new member of the N1/T1 RNase superfamily. BioMed Research International. https://doi.org/10.1155/2016/4239375.

  19. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680–685. https://doi.org/10.1038/227680a0.

    Article  Google Scholar 

  20. Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M. R., Appel, R. D., & Bairoch, A. (2005). Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook (pp. 571–607). New York: Humana Press. https://doi.org/10.1385/1-59259-584-7:531.

    Book  Google Scholar 

  21. Kozakov, D., Beglov, D., Bohnuud, T., Mottarella, S., Xia, B., Hall, D. R., & Vajda, S. (2013). How good is automated protein docking? Proteins: Structure, Function, and Bioinformatics, 81, 2159–2166. https://doi.org/10.1002/prot.24403.

    Article  Google Scholar 

  22. Guruprasad, K., Reddy, B. V. B., & Pandit, M. W. (1990). Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Engineering, 4, 155–161. https://doi.org/10.1093/protein/4.2.155.

    Article  Google Scholar 

  23. Ilinskaya, O., Ulyanova, V., Lisevich, I., Dudkina, E., Zakharchenko, N., Kusova, A., Faizullin, D., & Yu, Z. (2018). The native monomer of Bacillus pumilus ribonuclease does not exist extracellularly. BioMed Research International. https://doi.org/10.1155/2018/4837623.

  24. Dudkina, E., Ulyanova, V., & Ilinskaya, O. (2017). Balnase, a new dimer-forming ribonuclease from Bacillus altitudinis. BioNanoScience, 7, 127–129. https://doi.org/10.1007/s12668-016-0305-y.

    Article  Google Scholar 

  25. Schweisguth, D. C., Chelladurai, B. S., Nicholson, A. W., & Moore, P. B. (1994). Structural characterization of a ribonuclease III processing signal. Nucleic Acids Research, 22, 604–612. https://doi.org/10.1093/nar/22.4.604.

    Article  Google Scholar 

  26. Gotte, G., & Libonati, M. (2004). Oligomerization of ribonuclease A: two novel three-dimensional domain-swapped tetramers. The Journal of Biological Chemistry, 279, 36670–36679. https://doi.org/10.1074/jbc.M404780200.

    Article  Google Scholar 

  27. Ermakova, E. (2007). Brownian dynamics simulation of the competitive reactions: binase dimerization and the association of binase and barstar. Biophysical Chemistry, 130, 26–31. https://doi.org/10.1016/j.bpc.2007.06.012.

    Article  Google Scholar 

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Funding

The research was performed within the Russian Government Program of Competitive Growth of Kazan Federal University. Experiments to determine the structural features of new RNases have been supported by the Russian Science Foundation (Grant No. 18-74-00108). Cytotoxicity analysis was performed with the support of the Russian Foundation for Basic Research (Grant No. 17-00-00060).

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Authors and Affiliations

  1. Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str. 18, Kazan, 420008, Russia

    Yulia V. Surchenko, Elena V. Dudkina, Alsu I. Nadyrova, Vera V. Ulyanova, Pavel V. Zelenikhin & Olga N. Ilinskaya

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  1. Yulia V. Surchenko
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  2. Elena V. Dudkina
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  3. Alsu I. Nadyrova
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  4. Vera V. Ulyanova
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  5. Pavel V. Zelenikhin
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  6. Olga N. Ilinskaya
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Correspondence to Yulia V. Surchenko.

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Surchenko, Y.V., Dudkina, E.V., Nadyrova, A.I. et al. Cytotoxic Potential of Novel Bacillary Ribonucleases Balnase and Balifase. BioNanoSci. 10, 409–415 (2020). https://doi.org/10.1007/s12668-020-00720-6

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