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Melittin Interaction with Sulfated Cell Surface Sugars
Abstract
Melittin is a 26-residue cationic peptide with cytolytic and antimicrobial properties. Studies on the action mechanism of melittin have focused almost exclusively on the membrane-perturbing properties of this peptide, investigating in detail the melittin-lipid interaction. Here, we report physical-chemical studies on an alternative mechanism by which melittin could interact with the cell membrane. As the outer surface of many cells is decorated with anionic (sulfated) glycosaminoglycans (GAGs), a strong Coulombic interaction between the two oppositely charged molecules can be envisaged. Indeed, the present study using isothermal titration calorimetry reveals a high affinity of melittin for several GAGs, that is, heparan sulfate (HS), dermatan sulfate, and heparin. The microscopic binding constant of melittin for HS is 2.4 x 10 (5) M (-1), the reaction enthalpy is Delta H melittin (0) = -1.50 kcal/mol, and the peptide-to-HS stoichiometry is approximately 11 at 10 mM Tris, 100 mM NaCl at pH 7.4 and 28 degrees C. Delta H melittin (0) is characterized by a molar heat capacity of Delta C P (0) = -227 cal mol (-1) K (-1). The large negative heat capacity change indicates that hydrophobic interactions must also be involved in the binding of melittin to HS. Circular dichroism spectroscopy demonstrates that the binding of the peptide to HS induces a conformational change to a predominantly alpha-helical structure. A model for the melittin-HS complex is presented. Melittin binding was compared with that of magainin 2 and nisin Z to HS. Magainin 2 is known for its antimicrobial properties, but it does not cause lysis of the eukaryotic cells. Nisin Z shows activity against various Gram-positive bacteria. Isothermal titration calorimetry demonstrates that magainin 2 and nisin Z do not bind to HS (5-50 degrees C, 10 mM Tris, and 100 mM NaCl at pH 7.4).
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“analysis of the dependence of affinity constants on sodium chloride concentration (53, 54) indicated that the numbers of purely ionic interactions involved in the HS binding of apoE4 is about 3-fold larger than that for apoE3 (data not shown).”
From Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate: A Surface Plasmon Resonance Study (2008) · cites this paper as [54]
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Cites
Manning, G. S. (1978) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500002031 · Cited by 2,941
Zasloff, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.15.5449 · Cited by 2,305
Record, M. T., Anderson, C. F., & Lohman, T. M. (1978) · Quarterly Reviews of Biophysics · doi:10.1017/s003358350000202x · Cited by 1,681
Mode of action of membrane active antimicrobial peptides
Shai, Y. (2002) · Biopolymers · doi:10.1002/bip.10260 · Cited by 1,579
Habermann, E. (1972) · Science · doi:10.1126/science.177.4046.314 · Cited by 1,570
Barrel-Stave Model or Toroidal Model? A Case Study on Melittin Pores
Yang, L., Harroun, T. A., Weiss, T. M., Ding, L., & Huang, H. W. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)75802-x · Cited by 1,114
The actions of melittin on membranes
Dempsey, C. E. (1990) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(90)90006-x · Cited by 852
Luo, P., & Baldwin, R. L. (1997) · Biochemistry · doi:10.1021/bi9707133 · Cited by 643
Detergent-like actions of linear amphipathic cationic antimicrobial peptides
Bechinger, B., & Lohner, K. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.07.001 · Cited by 596
The structure of melittin. II. Interpretation of the structure.
Terwilliger, T. C., & Eisenberg, D. S. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)65098-0 · Cited by 503
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Survey of the year 2008: applications of isothermal titration calorimetry
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Yamauchi, Y., Deguchi, N., Takagi, C., Tanaka, M., Dhanasekaran, P., Nakano, M., Handa, T., Phillips, M. C., Lund-Katz, S., & Saito, H. (2008) · Biochemistry · doi:10.1021/bi8003999 · Cited by 53
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Sun, J. L., Yu, J.-S., Yu, Z., Zha, X., & Wu, Y. (2011) · The Journal of Chemical Thermodynamics · doi:10.1016/j.jct.2011.10.003 · Cited by 7
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Kim, C., Kim, D. S., Nam, D., Kim, S., Shim, B. S., & Ahn, K. S. (2014) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-014-0172-4 · Cited by 4
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[A short discharge letter with a copy to the patient--satisfactory for patients and practitioners].
Nielsen, F. T., Rosholm, J.-U., Søndergaard, J., Gohr, T., & Tougaard, L. (1994) · PubMed · Cited by 3
Teixeira-Cruz, J. M., Martins-Ferreira, J., Monteiro‐Machado, M., Strauch, M. A., Moraes, J. A., Amaral, L. S., Valente, R. D. C., Melo, P. A., & Quintas, L. E. M. (2022) · Toxicon · doi:10.1016/j.toxicon.2022.107011 · Cited by 2
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Phoenix, D. A., Dennison, S. R., & Harris, F. (2013) · Wiley eBooks · doi:10.1002/9783527652853.ch6 · Cited by 2
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Zehender, F. (2012) · edoc (University of Basel) · doi:10.5451/unibas-006077400
Impact of hyperlipidaemia on the orbital bone cefotaxime levels in rats
Panitsa, G., Panitsas, A., Potamianou, A., Messari, J., Vovou, J., & Tesseromatis, C. (2010) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-010-0004-y
Ahl, I.-M. (2010)
Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain
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Metadata
- Authors
- Klocek, G., & Seelig, J.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Seelig, Joachim
- ORCID
- Seelig, Joachim
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-01-26
- Volume
- 47
- Issue
- 9
- Pages
- 2841-2849
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W1975967141
- Cited by
- 60
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 3 · 2016: 6 · 2015: 1 · 2014: 7 · 2013: 6 · 2012: 3
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Pharmacology (medical) › Healthcare and Venom Research
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › thermodynamics and calorimetric analyses
- Keywords
- melittin, heparan sulfate, sulfated glycosaminoglycans, cationic antimicrobial peptides, peptide conformational change, alpha-helix, binding enthalpy, hydrophobic interactions, magainin 2, nisin Z, heparin, dermatan sulfate, cell membrane interaction
- MeSH terms
- Calorimetry, Circular Dichroism, Glycosaminoglycans, Heparan Sulfate, Hydrogen-Ion Concentration, Melitten, Models, Biological, Nisin, Protein Binding, Protein Structure, Secondary
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