Skip to main content
SpringerLink
Log in

Interaction of aurein 1.2 and its analogue with DPPC lipid bilayer

  • Original Paper
  • Published:
Journal of Biological Physics Aims and scope Submit manuscript

Abstract

Antibacterial peptides have potential as novel therapeutic agents for bacterial infections. Aurein 1.2 is one of the smallest antibacterial peptides extracted from an anuran. LLAA is a more active analogue of aurein 1.2. Antibacterial peptides usually accomplish their function by interacting with bacterial membrane selectively. In this study, we tried to find the reasons for the stronger antibacterial activity of LLAA compared with aurein 1.2. For this purpose, the interaction of aurein 1.2 and LLAA with dipalmitoylphosphatidylcholine (DPPC) was investigated by molecular dynamics (MD) simulation. In addition, the structure of peptides and their antibacterial activity were investigated by circular dichroism (CD) and dilution test method, respectively. MD results showed that LLAA is more flexible compared with aurein 1.2. Furthermore, LLAA loses its structure more than aurein 1.2 in the DPPC bilayer. A higher amount of water molecules penetrate into bilayer in the presence of LLAA relative to aurein 1.2. According to the antibacterial result that indicated LLAA is remarkably more active than aurein 1.2, it can be concluded that flexibility of the peptide is a determining factor in antibacterial activity. Probably, flexibility of the peptides facilitates formation of effective pores in the lipid bilayer.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Bahar, A.A., Ren, D.: Antimicrobial peptides. Pharmaceuticals 6(12), 1543–1575 (2013)

    Article  Google Scholar 

  2. Yeung, A.T., Gellatly, S.L., Hancock, R.E.: Multifunctional cationic host defence peptides and their clinical applications. Cell. Mol. Life Sci. 68(13), 2161–2176 (2011)

    Article  Google Scholar 

  3. Hoskin, D.W., Ramamoorthy, A.: Studies on anticancer activities of antimicrobial peptides. Biochim. Biophys. Acta. 1778(2), 357–375 (2008)

    Article  Google Scholar 

  4. Al-Benna, S., Shai, Y., Jacobsen, F., Steinstraesser, L.: Oncolytic activities of host defense peptides. Int. J. Mol. Sci. 12(11), 8027–8051 (2011)

    Article  Google Scholar 

  5. Yates, C., Sharp, S., Jones, J., Topps, D., Coleman, M., Aneja, R., Jaynes, J., Turner, T.: LHRH-conjugated lytic peptides directly target prostate cancer cells. Biochem. Pharmacol. 81(1), 104–110 (2011)

    Article  Google Scholar 

  6. Wang, G., Li, X., Wang, Z.: APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res. 37(suppl 1), D933–D937 (2009)

    Article  Google Scholar 

  7. Zasloff, M.: Antimicrobial peptides of multicellular organisms. Nature 415(6870), 389–395 (2002)

    Article  ADS  Google Scholar 

  8. Brogden, K.A.: Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3(3), 238–250 (2005)

    Article  Google Scholar 

  9. Legrand, B., Mathieu, L., Lebrun, A., Andriamanarivo, S., Lisowski, V., Masurier, N., Zirah, S., Kang, Y.K., Martinez, J., Maillard, L.T.: Thiazole-based γ-building blocks as reverse-turn mimetic to design a gramicidin S analogue: conformational and biological evaluation. Chem. Eur. J. 20(22), 6713–6720 (2014)

    Article  Google Scholar 

  10. Rozek, T., Wegener, K.L., Bowie, J.H., Olver, I.N., Carver, J.A., Wallace, J.C., Tyler, M.J.: The antibiotic and anticancer active aurein peptides from the Australian bell frogs Litoria aurea and Litoria raniformis. Eur. J. Biochem. 267(17), 5330–5341 (2000)

    Article  Google Scholar 

  11. Boland, M.P., Separovic, F.: Membrane interactions of antimicrobial peptides from Australian tree frogs. Biochim. Biophys. Acta. 1758(9), 1178–1183 (2006)

    Article  Google Scholar 

  12. Wang, G., Li, Y., Li, X.: Correlation of three-dimensional structures with the antibacterial activity of a group of peptides designed based on a nontoxic bacterial membrane anchor. J. Biol. Chem. 280(7), 5803–5811 (2005)

    Article  Google Scholar 

  13. Strömstedt, A.A., Ringstad, L., Schmidtchen, A., Malmsten, M.: Interaction between amphiphilic peptides and phospholipid membranes. Curr. Opin. Colloid Interface Sci. 15(6), 467–478 (2010)

    Article  Google Scholar 

  14. Li, X., Li, Y., Peterkofsky, A., Wang, G.: NMR studies of aurein 1.2 analogs. Biochim. Biophys. Acta (BBA) - Biomembr. 1758(9), 1203–1214 (2006)

    Article  Google Scholar 

  15. Tieleman, D.P., Berendsen, H.: Molecular dynamics simulations of a fully hydrated dipalmitoylphosphatidylcholine bilayer with different macroscopic boundary conditions and parameters. J. Chem. Phys. 105(11), 4871–4880 (1996)

    Article  ADS  Google Scholar 

  16. Kandt, C., Ash, W.L., Tieleman, D.P.: Setting up and running molecular dynamics simulations of membrane proteins. Methods 41(4), 475–488 (2007)

    Article  Google Scholar 

  17. Mark, P., Nilsson, L.: Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. A 105(43), 9954–9960 (2001)

    Article  Google Scholar 

  18. Hess, B., Kutzner, C., Van Der Spoel, D., Lindahl, E.: GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4(3), 435–447 (2008)

    Article  Google Scholar 

  19. Hess, B., Bekker, H., Berendsen, H.J., Fraaije, J.G.: LINCS: a linear constraint solver for molecular simulations. J. Comput. Chem. 18(12), 1463–1472 (1997)

    Article  Google Scholar 

  20. Poger, D., Van Gunsteren, W.F., Mark, A.E.: A new force field for simulating phosphatidylcholine bilayers. J. Comput. Chem. 31(6), 1117–1125 (2010)

    Article  Google Scholar 

  21. Essmann, U., Perera, L., Berkowitz, M.L., Darden, T., Lee, H., Pedersen, L.G.: A smooth particle mesh Ewald method. J. Chem. Phys. 103(19), 8577–8593 (1995)

    Article  ADS  Google Scholar 

  22. Nosé, S.: A unified formulation of the constant temperature molecular dynamics methods. J. Chem. Phys. 81(1), 511–519 (1984)

    Article  ADS  Google Scholar 

  23. Hoover, W.G.: Canonical dynamics: equilibrium phase-space distributions. Phys. Rev. A 31(3), 1695–1697 (1985)

    Article  ADS  Google Scholar 

  24. Nosé, S., Klein, M.L.: Constant pressure molecular dynamics for molecular systems. Mol. Phys. 50(5), 1055–1076 (1983)

    Article  ADS  Google Scholar 

  25. Kabsch, W., Sander, C.: Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22(12), 2577–2637 (1983)

    Article  Google Scholar 

  26. Joosten, R.P., Te Beek, T.A., Krieger, E., Hekkelman, M.L., Hooft, R.W., Schneider, R., Sander, C., Vriend, G.: A series of PDB related databases for everyday needs. Nucleic Acids Res. 39(suppl 1), D411–D419 (2011)

    Article  Google Scholar 

  27. Kelly, S.M., Price, N.C.: The use of circular dichroism in the investigation of protein structure and function. Curr. Protein Pept. Sci. 1(4), 349–384 (2000)

    Article  Google Scholar 

  28. Mosmann, T.: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65(1–2), 55–63 (1983)

    Article  Google Scholar 

  29. Khandelia, H., Duelund, L., Pakkanen, K.I., Ipsen, J.H.: Triglyceride blisters in lipid bilayers: implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes. PLoS ONE 5(9), e12811 (2010). doi:10.1371/journal.pone.0012811

    Article  ADS  Google Scholar 

  30. Shiraki, K., Nishikawa, K., Goto, Y.: Trifluoroethanol-induced stabilization of the α-helical structure of β-lactoglobulin: implication for non-hierarchical protein folding. J. Mol. Biol. 245(2), 180–194 (1995)

    Article  Google Scholar 

Download references

Acknowledgments

Financial support provided by the Research Council of the Institute for Advanced Studies in Basic Sciences is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45137-66731, Iran

    Zahra Sajjadiyan, Nasim Cheraghi, Sarah Mohammadinejad & Leila Hassani

Authors
  1. Zahra Sajjadiyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nasim Cheraghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Mohammadinejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leila Hassani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah Mohammadinejad.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sajjadiyan, Z., Cheraghi, N., Mohammadinejad, S. et al. Interaction of aurein 1.2 and its analogue with DPPC lipid bilayer. J Biol Phys 43, 127–137 (2017). https://doi.org/10.1007/s10867-016-9438-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10867-016-9438-z

Keywords

Search

Navigation