Antimicrobial C3a –Biology, Biophysics, and Evolution

  • Martin Malmsten
  • Artur Schmidtchen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 598)


Atopic Dermatitis Antimicrobial Peptide Helical Region Mast Cell Tryptase Candida Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andersson, E., Rydengard, V., Sonesson, A., Morgelin, M., Bjorck, L., and Schmidtchen, A. (2004) Antimicrobial activities of heparin-binding peptides. Eur J Biochem 271: 1219-1226.PubMedCrossRefGoogle Scholar
  2. Baev, D., Li, X.S., Dong, J., Keng, P., and Edgerton, M. (2002) Human salivary histatin 5 causes disordered volume regulation and cell cycle arrest in Candida albicans. Infect Immun 70: 4777-4784.PubMedCrossRefGoogle Scholar
  3. Boman, H.G., Agerberth, B., and Boman, A. (1993) Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine. Infect Immun 61: 2978-2984.PubMedGoogle Scholar
  4. Brogden, K.A. (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3: 238-250.PubMedCrossRefGoogle Scholar
  5. Bulet, P., Stocklin, R., and Menin, L. (2004) Anti-microbial peptides: from invertebrates to vertebrates. Immunol Rev 198: 169-184.PubMedCrossRefGoogle Scholar
  6. Caporale, L.H., Tippett, P.S., Erickson, B.W., and Hugli, T.E. (1980) The active site of C3a anaphylatoxin. J Biol Chem 255: 10758-10763.PubMedGoogle Scholar
  7. Den Hertog, A.L., Wong Fong Sang, H.W., Kraayenhof, R., Bolscher, J.G., Van’t Hof, W., Veerman, E.C., and Nieuw Amerongen, A.V. (2004) Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization. Biochem J 379: 665-672.CrossRefGoogle Scholar
  8. Epand, R.F., Ramamoorthy, A., and Epand, R.M. (2006) Membrane lipid composition and the interaction of pardaxin: the role of cholesterol. Protein Pept Lett 13: 1-5.PubMedCrossRefGoogle Scholar
  9. Ganz, T. (2001) Antimicrobial proteins and peptides in host defense. Semin Respir Infect 16: 4-10.PubMedCrossRefGoogle Scholar
  10. Glukhov, E., Stark, M., Burrows, L.L., and Deber, C.M. (2005) Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes. J Biol Chem 280: 33960-33967.PubMedCrossRefGoogle Scholar
  11. Hallock, K.J., Lee, D.K., Omnaas, J., Mosberg, H.I., and Ramamoorthy, A. (2002) Membrane composition determines pardaxin’s mechanism of lipid bilayer disruption. Biophys J 83: 1004-1013.PubMedGoogle Scholar
  12. Huber, R., Scholze, H., Paques, E.P., and Deisenhofer, J. (1980) Crystal structure analysis and molecular model of human C3a anaphylatoxin. Hoppe Seylers Z Physiol Chem 361: 1389-1399.Google Scholar
  13. Hugli, T.E. (1990) Structure and function of C3a anaphylatoxin. Curr Top Microbiol Immunol 153: 181-208.PubMedGoogle Scholar
  14. Janssen, B.J., Huizinga, E.G., Raaijmakers, H.C., Roos, A., Daha, M.R., Nilsson-Ekdahl, K., Nilsson, B., and Gros, P. (2005) Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437: 505-511.PubMedCrossRefGoogle Scholar
  15. Kawamoto, S., Yalcindag, A., Laouini, D., Brodeur, S., Bryce, P., Lu, B., Humbles, A.A., Oettgen, H., Gerard, C., and Geha, R.S. (2004) The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest 114: 399-407.PubMedCrossRefGoogle Scholar
  16. Koshlukova, S.E., Lloyd, T.L., Araujo, M.W., and Edgerton, M. (1999) Salivary histatin 5 induces non-lytic release of ATP from Candida albicans leading to cell death. J Biol Chem 274: 18872-18879.PubMedCrossRefGoogle Scholar
  17. Kozel, T.R. (1996) Activation of the complement system by pathogenic fungi. Clin Microbiol Rev 9: 34-46.PubMedGoogle Scholar
  18. Kozel, T.R., Weinhold, L.C., and Lupan, D.M. (1996) Distinct characteristics of initiation of the classical and alternative complement pathways by Candida albicans. Infect Immun 64: 3360-3368.PubMedGoogle Scholar
  19. Lee, M.T., Hung, W.C., Chen, F.Y., and Huang, H.W. (2005) Many-body effect of antimicrobial peptides: on the correlation between lipid’s spontaneous curvature and pore formation. Biophys J 89: 4006-4016.PubMedCrossRefGoogle Scholar
  20. Lehrer, R.I., and Ganz, T. (2002) Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9: 18-22.PubMedCrossRefGoogle Scholar
  21. Lohner, K., and Blondelle, S.E. (2005) Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. Comb Chem High Throughput Screen 8: 241-256.PubMedCrossRefGoogle Scholar
  22. Lu, Z.X., Fok, K.F., Erickson, B.W., and Hugli, T.E. (1984) Conformational analysis of COOH-terminal segments of human C3a. Evidence of ordered conformation in an active 21-residue peptide. J Biol Chem 259: 7367-7370.PubMedGoogle Scholar
  23. Maxwell, A.I., Morrison, G.M., and Dorin, J.R. (2003) Rapid sequence divergence in mammalian beta-defensins by adaptive evolution. Mol Immunol 40: 413-421.PubMedCrossRefGoogle Scholar
  24. Nonaka, M., and Yoshizaki, F. (2004) Evolution of the complement system. Mol Immunol 40: 897-902.PubMedCrossRefGoogle Scholar
  25. Nordahl, E.A., Rydengard, V., Nyberg, P., Nitsche, D.P., Morgelin, M., Malmsten, M., Bjorck, L., and Schmidtchen, A. (2004) Activation of the complement system generates antibacterial peptides. Proc Natl Acad Sci U S A 101: 16879-16884.PubMedCrossRefGoogle Scholar
  26. Odds, F.C. (1988) Candida and candidosis. London ; Philadelphia: Bailliére Tindall.Google Scholar
  27. Ohki, S., Marcus, E., Sukumaran, D.K., and Arnold, K. (1994) Interaction of melittin with lipid membranes. Biochim Biophys Acta 1194: 223-232.PubMedCrossRefGoogle Scholar
  28. Opekarova, M., and Tanner, W. (2003) Specific lipid requirements of membrane proteins–a putative bottleneck in heterologous expression. Biochim Biophys Acta 1610: 11-22.PubMedCrossRefGoogle Scholar
  29. Pasupuleti, M., Walse, B., Nordahl, E.A., Morgelin, M., Malmsten, M., and Schmidtchen, A. (2006) Preservation of antimicrobial properties of complement peptide C3a - from invertebrates to humans. J Biol Chem.Google Scholar
  30. Pinto, M.R., Chinnici, C.M., Kimura, Y., Melillo, D., Marino, R., Spruce, L.A., De Santis, R., Parrinello, N., and Lambris, J.D. (2003) CiC3-1a-mediated chemotaxis in the deuterostome invertebrate Ciona intestinalis (Urochordata). J Immunol 171: 5521-5528.PubMedGoogle Scholar
  31. Pitarch, A., Sanchez, M., Nombela, C., and Gil, C. (2003) Analysis of the Candida albicans proteome. II. Protein information technology on the Net (update 2002). J Chromatogr B Analyt Technol Biomed Life Sci 787: 129-148.PubMedCrossRefGoogle Scholar
  32. Powers, J.P., and Hancock, R.E. (2003) The relationship between peptide structure and antibacterial activity. Peptides 24: 1681-1691.PubMedCrossRefGoogle Scholar
  33. Ringstad, L., Andersson Nordahl, E., Schmidtchen, A., and Malmsten, M. (2007) Composition Effect on Peptide Interaction with Lipids and Bacteria: Variants of C3a Peptide CNY21. Biophys J 92: 87-98.PubMedCrossRefGoogle Scholar
  34. Savolainen, J., Lammintausta, K., Kalimo, K., and Viander, M. (1993) Candida albicans and atopic dermatitis. Clin Exp Allergy 23: 332-339.PubMedCrossRefGoogle Scholar
  35. Schwartz, L.B., Kawahara, M.S., Hugli, T.E., Vik, D., Fearon, D.T., and Austen, K.F. (1983) Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. J Immunol 130: 1891-1895.PubMedGoogle Scholar
  36. Selsted, M.E., Brown, D.M., DeLange, R.J., Harwig, S.S., and Lehrer, R.I. (1985) Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils. J Biol Chem 260: 4579-4584.PubMedGoogle Scholar
  37. Selsted, M.E., Harwig, S.S., Ganz, T., Schilling, J.W., and Lehrer, R.I. (1985) Primary structures of three human neutrophil defensins. J Clin Invest 76: 1436-1439.PubMedGoogle Scholar
  38. Semple, C.A., Rolfe, M., and Dorin, J.R. (2003) Duplication and selection in the evolution of primate beta-defensin genes. Genome Biol 4: R31.PubMedCrossRefGoogle Scholar
  39. Shai, Y. (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66: 236-248.PubMedCrossRefGoogle Scholar
  40. Skarnes, R.C., and Watson, D.W. (1957) Antimicrobial factors of normal tissues and fluids. Bacteriol Rev 21: 273-294.PubMedGoogle Scholar
  41. Sohnle, P.G., and Kirkpatrick, C.H. (1976) Deposition of complement in the lesions of experimental cutaneous candidiasis in guinea pigs. J Cutan Pathol 3: 232-238.PubMedCrossRefGoogle Scholar
  42. Sonesson, A., Ringstad, L., Andersson Nordahl, E., Malmsten, M., Morgelin, M., and Schmidtchen, A. (2006) Antifungal activity of C3a and C3a-derived peptides against Candida. Biochim Biophys Acta.Google Scholar
  43. Steiner, H., Hultmark, D., Engström, A., Bennich, H., and Boman, H.G. (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292: 246-248.PubMedCrossRefGoogle Scholar
  44. Sunyer, J.O., Boshra, H., and Li, J. (2005) Evolution of anaphylatoxins, their diversity and novel roles in innate immunity: insights from the study of fish complement. Vet Immunol Immunopathol 108: 77-89.PubMedCrossRefGoogle Scholar
  45. Taylor, J.C., Crawford, I.P., and Hugli, T.E. (1977) Limited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE): partial characterization of C3 fragments. Biochemistry 16: 3390-3396.PubMedCrossRefGoogle Scholar
  46. Tennessen, J.A. (2005) Molecular evolution of animal antimicrobial peptides: widespread moderate positive selection. J Evol Biol 18: 1387-1394.PubMedCrossRefGoogle Scholar
  47. Wang, Y., Agerberth, B., Lothgren, A., Almstedt, A., and Johansson, J. (1998) Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37. J Biol Chem 273: 33115-33118.PubMedCrossRefGoogle Scholar
  48. Werfel, T., Kirchhoff, K., Wittmann, M., Begemann, G., Kapp, A., Heidenreich, F., Gotze, O., and Zwirner, J. (2000) Activated human T lymphocytes express a functional C3a receptor. J Immunol 165: 6599-6605.PubMedGoogle Scholar
  49. Williamson, M.P., and Madison, V.S. (1990) Three-dimensional structure of porcine C5adesArg from 1H nuclear magnetic resonance data. Biochemistry 29: 2895-2905.PubMedCrossRefGoogle Scholar
  50. Wright, J., Schwartz, J.H., Olson, R., Kosowsky, J.M., and Tauber, A.I. (1986) Proton secretion by the sodium/hydrogen ion antiporter in the human neutrophil. J Clin Invest 77: 782-788.PubMedCrossRefGoogle Scholar
  51. Yount, N.Y., Bayer, A.S., Xiong, Y.Q., and Yeaman, M.R. (2006) Advances in antimicrobial peptide immunobiology. Biopolymers.Google Scholar
  52. Zasloff, M. (1987) Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A 84: 5449-5453.PubMedCrossRefGoogle Scholar
  53. Zasloff, M. (2002) Antimicrobial peptides of multicellular organisms. Nature 415: 389-395.PubMedCrossRefGoogle Scholar
  54. Zelezetsky, I., Pontillo, A., Puzzi, L., Antcheva, N., Segat, L., Pacor, S., Crovella, S., and Tossi, A. (2006a) Evolution of the primate cathelicidin - correlation between structural variations and antimicrobial activity. J Biol Chem.Google Scholar
  55. Zelezetsky, I., and Tossi, A. (2006b) Alpha-helical antimicrobial peptides-Using a sequence template to guide structure-activity relationship studies. Biochim Biophys Acta.Google Scholar
  56. Zeya, H.I., and Spitznagel, J.K. (1963) Antibacterial and Enzymic Basic Proteins from Leukocyte Lysosomes: Separation and Identification. Science 142: 1085-1087.PubMedCrossRefGoogle Scholar
  57. Zhang, L., and Falla, T.J. (2004) Cationic antimicrobial peptides - an update. Expert Opin Investig Drugs 13: 97-106.PubMedCrossRefGoogle Scholar
  58. Zhang, X., Boyar, W., Toth, M.J., Wennogle, L., and Gonnella, N.C. (1997) Structural definition of the C5a C terminus by two-dimensional nuclear magnetic resonance spectroscopy. Proteins 28: 261-267.PubMedCrossRefGoogle Scholar
  59. Zhu, Y., Thangamani, S., Ho, B., and Ding, J.L. (2005) The ancient origin of the complement system. Embo J 24: 382-394.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Martin Malmsten
    • 1
  • Artur Schmidtchen
    • 2
  1. 1.Department of PharmacyUppsala UniversitySE-751 23 UppsalaSweden
  2. 2.Section of Dermatology and Venereology, Department of Clinical Sciences Biomedical CenterLund UniversitySE-221 84 Lund

Personalised recommendations