Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Structural and Functional Characterization of CRAMP-18 Derived from a Cathelicidin-Related Antimicrobial Peptide CRAMP

  • Park, Kyong-Soo (Department of Chemistry, Konkuk University) ;
  • Shin, Song-Yub (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Hahm, Kyung-Soo (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Kim, Yang-Mee (Department of Chemistry, Konkuk University)
  • Published : 2003.10.20
Download PDF
⟨ Previous Next ⟩

Abstract

CRAMP was identified from a cDNA clone derived from a mouse femoral marrow cells as a member of cathelicidin-derived antimicrobial peptide. Tertiary structure of CRAMP in TFE/$H_2O$ (1 : 1, v/v) solution has been determined by NMR spectroscopy previously and consists of two amphipathic $\alpha-helices$ from Leu4 to Lys10 and from Gly16 to Leu33. These two helices are connected by a flexible region from Gly11 to Gly16. Analysis of series of fragments composed of various portion of CRAMP revealed that an 18-residue fragment with the sequence from Gly16 to Leu33 (CRAMP-18) was found to retain antibacterial activity without cytotoxicity. The effects of two Phe residues at positions 14 and 15 of CRAMP-18 on structure, antibacterial activity, and interaction with lipid membranes were investigated by $Phe^{14,15}$ ${\rightarrow}$ Ala substitution (CRAMP-18-A) in the present study. Substitution of Phe with Ala in CRAMP-18 caused a significant reduction on antibacterial and membrane-disrupting activities. Tertiary structures of CRAMP-18 in 50% TFE/$H_2O$ (1 : 1, v : v) solution shows amphipathic ${\alpha}$-helix, from $Glu^2{\;}to{\;}Leu^{18}$, while CRAMP-18-A has relatively short amphipathic ${\alpha}$-helix from $Leu^4{\;}to{\;}Ala^{15}$. These results suggest that the hydrophobic property of $Phe^{14}{\;}and{\;}Phe^15$ in CRAMP-18 is essential for its antibacterial activity, ${\alpha}$-helical structure, and interactions with phospholipid membranes.

Keywords

References

  1. Zaiou, M.; Gallo, R. L. J. Mol. Med. 2002, 80, 549. https://doi.org/10.1007/s00109-002-0350-6
  2. Boman, H. G. Scand. J. Immunol. 1998, 48, 15. https://doi.org/10.1046/j.1365-3083.1998.00343.x
  3. Lehrer, R. I.; Ganz, T. Curr. Opin. Immunol. 1999, 11, 23. https://doi.org/10.1016/S0952-7915(99)80005-3
  4. Maloy, W. L.; Kari, U. P. Biopolymers 1995, 37, 105. https://doi.org/10.1002/bip.360370206
  5. Martin, E.; Ganz, T.; Lehrer, R. I. J. Leukoc. Biol. 1995, 58, 128.
  6. Zanetti, M.; Gennaro, R.; Romeo, D. Ann. N. Y. Acad. Sci. 1997,832, 147. https://doi.org/10.1111/j.1749-6632.1997.tb46244.x
  7. Zanetti, M.; Gennaro, R.; Romeo, D. FEBS Lett. 1995, 374, 1. https://doi.org/10.1016/0014-5793(95)01050-O
  8. Gennaro, R.; Zanetti, M. Biopolymers 2000, 55, 31. https://doi.org/10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9
  9. Gallo, R. L.; Kim, K. J. J. Biol. Chem. 1997, 272, 13088. https://doi.org/10.1074/jbc.272.20.13088
  10. Ha, J. M.; Shin, S. Y.; Kang, S. W. Bull. Korean Chem. Soc. 1999,20, 1073. https://doi.org/10.1007/BF02706938
  11. Yu, K.; Park, K.; Kang, S. W.; Shin, S. Y.; Hahm, K. S.; Kim, Y. J.Pept. Res. 2002, 60, 1. https://doi.org/10.1034/j.1399-3011.2002.01968.x
  12. Atherton, E.; Logan, C. J.; Sheppard, R. C. J. Chem. Soc. Perkin.Trans. I 1981, 20, 538.
  13. Derome, A.; Williamson, M. J. Magn. Reson. 1990, 88, 177.
  14. Bax, A.; Davis, D. G. J. Magn. Reson. 1985, 65, 355.
  15. Macura, S.; Ernst, R. R. Mol. Phys. 1980, 41, 95. https://doi.org/10.1080/00268978000102601
  16. Bax, A.; Davis, D. G. J. Magn. Reson. 1985, 63, 207.
  17. Marion, D.; Wüthrich, K. Biochem. Biophys. Res. Commun. 1983,113, 967. https://doi.org/10.1016/0006-291X(83)91093-8
  18. Kim, Y.; Prestegard, J. P. J. Magn. Reson. 1989, 84, 9.
  19. Hicks, R. P.; Beard, D. J.; Young, J. K. Biopolymers 1992, 32, 85. https://doi.org/10.1002/bip.360320111
  20. Clore, G. M.; Gronenborn, A. M. CRC Crit. Rev. Biochem. Mol.Biol. 1989, 24, 479. https://doi.org/10.3109/10409238909086962
  21. Clore, G. M.; Gronenborn, A. M. Protein Sci. 1994, 3, 372.
  22. Brünger A.T. X-PLOR Manual, Version 3.1; Yale University: NewHaven, CT, 1993.
  23. Wuthrich, K.; Billeter, M.; Braun, W. J. Mol. Biol. 1983, 169,949. https://doi.org/10.1016/S0022-2836(83)80144-2
  24. Clore, G. M.; Gronenborn, A. M.; Nilges, M.; Ryan, C. A.Biochemistry 1987, 26, 8012. https://doi.org/10.1021/bi00398a069
  25. Nilges, M.; Clore, G. M.; Gronenborn, A. M. FEBS Lett. 1988,229, 317. https://doi.org/10.1016/0014-5793(88)81148-7
  26. Kuszewski, J.; Nilges, M.; Brünger, A. T. J. Biomol. NMR 1992, 2,33. https://doi.org/10.1007/BF02192799
  27. Wuthrich, K. NMR of Protein and Nucleic Acid; Wiley-Interscience: New York, 1986.
  28. Baxter, N. J.; Williamson, M. P. J. Biomol. NMR 1997, 9, 359. https://doi.org/10.1023/A:1018334207887
  29. Wishart, D. S.; Sykes, B. D.; Richards, F. M. Biochemistry 1992,31, 1647. https://doi.org/10.1021/bi00121a010
  30. Bang, E.; Lee, C.; Yoon, J.; Chung, J.; Lee, D.; Lee, W. Bull.Korean Chem. Soc. 2001, 2(5), 507.
  31. Yu, K.; Kang, S.; Kim, S.; Ryu, P.; Kim, Y. Journal ofBiomolecular Structure and Dynamics 2001, 18(4), 595. https://doi.org/10.1080/07391102.2001.10506691
  32. Park, K.; Baek, D.; Lim, D.; Park, S.; Kim, M.; Park, Y.; Kim, Y.Bull. Korean Chem. Soc. 2001, 22, 984.

Cited by

  1. Design and Synthesis of Antibacterial Pseudopeptides with a Potent Antibacterial Activity and More Improved Stability from a Short Cationic Antibacterial Peptide vol.26, pp.1, 2005, https://doi.org/10.5012/bkcs.2005.26.1.161
  2. Liquid Crystal-based Imaging of Enzymatic Reactions at Aqueous-liquid Crystal Interfaces Decorated with Oligopeptide Amphiphiles vol.31, pp.5, 2003, https://doi.org/10.5012/bkcs.2010.31.5.1262
  3. A Novel Trp-rich Model Antimicrobial Peptoid with Increased Protease Stability vol.31, pp.9, 2003, https://doi.org/10.5012/bkcs.2010.31.9.2509
  4. Pseudo-peptides as novel antileptospiral agents: Synthesis and spectral characterization vol.118, pp.None, 2014, https://doi.org/10.1016/j.saa.2013.09.105
  5. Indole moiety induced biological potency in pseudo-peptides derived from 2-amino-2-(1H-indole-2-yl) based acetamides: Chemical synthesis, in vitro anticancer activity and theoretical studies vol.1217, pp.None, 2020, https://doi.org/10.1016/j.molstruc.2020.128445