Skip to main content
NCBI home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1997 Dec;6(12):2631–2635. doi: 10.1002/pro.5560061216

alpha-Hemolysin, gamma-hemolysin, and leukocidin from Staphylococcus aureus: distant in sequence but similar in structure.

E Gouaux 1, M Hobaugh 1, L Song 1
PMCID: PMC2143621  PMID: 9416613

Abstract

alpha-Hemolysin from Staphylococcus aureus assembles from a water-soluble, monomeric species to a membrane-bound heptamer on the surface of target cells, creating water-filled channels that lead to cell death and lysis. Staphylococcus aureus also produces the gamma-hemolysin and leukocidin toxins, which function as two component toxins in the disruption and lysis of erythrocytes and leukocytes. Analysis of the aligned sequences of alpha-hemolysin, gamma-hemolysin, and leukocidin in the context of the alpha-hemolysin heptamer structure supports the conclusion that even though the level of sequence identity between alpha-hemolysin and the gamma-hemolysin and leukocidin toxins is in the so-called twilight zone, the three-dimensional structures of the protomers are probably conserved. By analogy with alpha-hemolysin, gamma-hemolysin and leukocidin may also form oligomeric, transmembrane channels in which an antiparallel beta-barrel constitutes the primary membrane-embedded domain.

Full Text

The Full Text of this article is available as a PDF (6.4 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhakdi S., Bayley H., Valeva A., Walev I., Walker B., Kehoe M., Palmer M. Staphylococcal alpha-toxin, streptolysin-O, and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins. Arch Microbiol. 1996 Feb;165(2):73–79. doi: 10.1007/s002030050300. [DOI] [PubMed] [Google Scholar]
  2. Bhakdi S., Muhly M., Korom S., Hugo F. Release of interleukin-1 beta associated with potent cytocidal action of staphylococcal alpha-toxin on human monocytes. Infect Immun. 1989 Nov;57(11):3512–3519. doi: 10.1128/iai.57.11.3512-3519.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhakdi S., Muhly M., Mannhardt U., Hugo F., Klapettek K., Mueller-Eckhardt C., Roka L. Staphylococcal alpha toxin promotes blood coagulation via attack on human platelets. J Exp Med. 1988 Aug 1;168(2):527–542. doi: 10.1084/jem.168.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhakdi S., Tranum-Jensen J. Alpha-toxin of Staphylococcus aureus. Microbiol Rev. 1991 Dec;55(4):733–751. doi: 10.1128/mr.55.4.733-751.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bjellqvist B., Basse B., Olsen E., Celis J. E. Reference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions. Electrophoresis. 1994 Mar-Apr;15(3-4):529–539. doi: 10.1002/elps.1150150171. [DOI] [PubMed] [Google Scholar]
  6. Bjellqvist B., Hughes G. J., Pasquali C., Paquet N., Ravier F., Sanchez J. C., Frutiger S., Hochstrasser D. The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences. Electrophoresis. 1993 Oct;14(10):1023–1031. doi: 10.1002/elps.11501401163. [DOI] [PubMed] [Google Scholar]
  7. Budarina Z. I., Sinev M. A., Mayorov S. G., Tomashevski A. Y., Shmelev I. V., Kuzmin N. P. Hemolysin II is more characteristic of Bacillus thuringiensis than Bacillus cereus. Arch Microbiol. 1994;161(3):252–257. doi: 10.1007/BF00248701. [DOI] [PubMed] [Google Scholar]
  8. Choorit W., Kaneko J., Muramoto K., Kamio Y. Existence of a new protein component with the same function as the LukF component of leukocidin or gamma-hemolysin and its gene in Staphylococcus aureus P83. FEBS Lett. 1995 Jan 9;357(3):260–264. doi: 10.1016/0014-5793(94)01372-8. [DOI] [PubMed] [Google Scholar]
  9. Cooney J., Kienle Z., Foster T. J., O'Toole P. W. The gamma-hemolysin locus of Staphylococcus aureus comprises three linked genes, two of which are identical to the genes for the F and S components of leukocidin. Infect Immun. 1993 Feb;61(2):768–771. doi: 10.1128/iai.61.2.768-771.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cribier B., Prévost G., Couppie P., Finck-Barbançon V., Grosshans E., Piémont Y. Staphylococcus aureus leukocidin: a new virulence factor in cutaneous infections? An epidemiological and experimental study. Dermatology. 1992;185(3):175–180. doi: 10.1159/000247443. [DOI] [PubMed] [Google Scholar]
  11. Fang Y., Cheley S., Bayley H., Yang J. The heptameric prepore of a staphylococcal alpha-hemolysin mutant in lipid bilayers imaged by atomic force microscopy. Biochemistry. 1997 Aug 5;36(31):9518–9522. doi: 10.1021/bi970600j. [DOI] [PubMed] [Google Scholar]
  12. Finck-Barbançon V., Duportail G., Meunier O., Colin D. A. Pore formation by a two-component leukocidin from Staphylococcus aureus within the membrane of human polymorphonuclear leukocytes. Biochim Biophys Acta. 1993 Oct 20;1182(3):275–282. doi: 10.1016/0925-4439(93)90069-d. [DOI] [PubMed] [Google Scholar]
  13. Gouaux J. E., Braha O., Hobaugh M. R., Song L., Cheley S., Shustak C., Bayley H. Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on membranes: a heptameric transmembrane pore. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12828–12831. doi: 10.1073/pnas.91.26.12828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hunter S. E., Brown J. E., Oyston P. C., Sakurai J., Titball R. W. Molecular genetic analysis of beta-toxin of Clostridium perfringens reveals sequence homology with alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus. Infect Immun. 1993 Sep;61(9):3958–3965. doi: 10.1128/iai.61.9.3958-3965.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jursch R., Hildebrand A., Hobom G., Tranum-Jensen J., Ward R., Kehoe M., Bhakdi S. Histidine residues near the N terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation. Infect Immun. 1994 Jun;62(6):2249–2256. doi: 10.1128/iai.62.6.2249-2256.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Krishnasastry M., Walker B., Braha O., Bayley H. Surface labeling of key residues during assembly of the transmembrane pore formed by staphylococcal alpha-hemolysin. FEBS Lett. 1994 Dec 12;356(1):66–71. doi: 10.1016/0014-5793(94)01240-7. [DOI] [PubMed] [Google Scholar]
  17. Lesieur C., Vécsey-Semjén B., Abrami L., Fivaz M., Gisou van der Goot F. Membrane insertion: The strategies of toxins (review). Mol Membr Biol. 1997 Apr-Jun;14(2):45–64. doi: 10.3109/09687689709068435. [DOI] [PubMed] [Google Scholar]
  18. Menzies B. E., Kernodle D. S. Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: role of histidines in toxin activity in vitro and in a murine model. Infect Immun. 1994 May;62(5):1843–1847. doi: 10.1128/iai.62.5.1843-1847.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Panchal R. G., Bayley H. Interactions between residues in staphylococcal alpha-hemolysin revealed by reversion mutagenesis. J Biol Chem. 1995 Sep 29;270(39):23072–23076. doi: 10.1074/jbc.270.39.23072. [DOI] [PubMed] [Google Scholar]
  20. Prevost G., Bouakham T., Piemont Y., Monteil H. Characterisation of a synergohymenotropic toxin produced by Staphylococcus intermedius. FEBS Lett. 1995 Dec 4;376(3):135–140. doi: 10.1016/0014-5793(95)01260-9. [DOI] [PubMed] [Google Scholar]
  21. Prévost G., Cribier B., Couppié P., Petiau P., Supersac G., Finck-Barbançon V., Monteil H., Piemont Y. Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect Immun. 1995 Oct;63(10):4121–4129. doi: 10.1128/iai.63.10.4121-4129.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rahman A., Izaki K., Kamio Y. Gamma-hemolysin genes in the same family with lukF and lukS genes in methicillin resistant Staphylococcus aureus. Biosci Biotechnol Biochem. 1993 Jul;57(7):1234–1236. doi: 10.1271/bbb.57.1234. [DOI] [PubMed] [Google Scholar]
  23. Rahman A., Nariya H., Izaki K., Kato I., Kamio Y. Molecular cloning and nucleotide sequence of leukocidin F-component gene (lukF) from methicillin resistant Staphylococcus aureus. Biochem Biophys Res Commun. 1992 Apr 30;184(2):640–646. doi: 10.1016/0006-291x(92)90637-z. [DOI] [PubMed] [Google Scholar]
  24. Smith R. F., Smith T. F. Automatic generation of primary sequence patterns from sets of related protein sequences. Proc Natl Acad Sci U S A. 1990 Jan;87(1):118–122. doi: 10.1073/pnas.87.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smith R. F., Smith T. F. Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling. Protein Eng. 1992 Jan;5(1):35–41. doi: 10.1093/protein/5.1.35. [DOI] [PubMed] [Google Scholar]
  26. Song L., Hobaugh M. R., Shustak C., Cheley S., Bayley H., Gouaux J. E. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science. 1996 Dec 13;274(5294):1859–1866. doi: 10.1126/science.274.5294.1859. [DOI] [PubMed] [Google Scholar]
  27. Supersac G., Prevost G., Piemont Y. Sequencing of leucocidin R from Staphylococcus aureus P83 suggests that staphylococcal leucocidins and gamma-hemolysin are members of a single, two-component family of toxins. Infect Immun. 1993 Feb;61(2):580–587. doi: 10.1128/iai.61.2.580-587.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suttorp N., Hessz T., Seeger W., Wilke A., Koob R., Lutz F., Drenckhahn D. Bacterial exotoxins and endothelial permeability for water and albumin in vitro. Am J Physiol. 1988 Sep;255(3 Pt 1):C368–C376. doi: 10.1152/ajpcell.1988.255.3.C368. [DOI] [PubMed] [Google Scholar]
  29. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tomita T., Kamio Y. Molecular biology of the pore-forming cytolysins from Staphylococcus aureus, alpha- and gamma-hemolysins and leukocidin. Biosci Biotechnol Biochem. 1997 Apr;61(4):565–572. doi: 10.1271/bbb.61.565. [DOI] [PubMed] [Google Scholar]
  31. Valeva A., Weisser A., Walker B., Kehoe M., Bayley H., Bhakdi S., Palmer M. Molecular architecture of a toxin pore: a 15-residue sequence lines the transmembrane channel of staphylococcal alpha-toxin. EMBO J. 1996 Apr 15;15(8):1857–1864. [PMC free article] [PubMed] [Google Scholar]
  32. WOODIN A. M. Purification of the two components of leucocidin from Staphylococcus aureus. Biochem J. 1960 Apr;75:158–165. doi: 10.1042/bj0750158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Walev I., Martin E., Jonas D., Mohamadzadeh M., Müller-Klieser W., Kunz L., Bhakdi S. Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions. Infect Immun. 1993 Dec;61(12):4972–4979. doi: 10.1128/iai.61.12.4972-4979.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Walker B., Krishnasastry M., Zorn L., Bayley H. Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin examined by truncation mutagenesis. J Biol Chem. 1992 Oct 25;267(30):21782–21786. [PubMed] [Google Scholar]
  35. Weiss M. S., Schulz G. E. Structure of porin refined at 1.8 A resolution. J Mol Biol. 1992 Sep 20;227(2):493–509. doi: 10.1016/0022-2836(92)90903-w. [DOI] [PubMed] [Google Scholar]
  36. Wimley W. C., White S. H. Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol. 1996 Oct;3(10):842–848. doi: 10.1038/nsb1096-842. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES