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. 1997 Jun 15;16(12):3426–3434. doi: 10.1093/emboj/16.12.3426

Aerolysin and pertussis toxin share a common receptor-binding domain.

J Rossjohn 1, J T Buckley 1, B Hazes 1, A G Murzin 1, R J Read 1, M W Parker 1
PMCID: PMC1169968  PMID: 9218785

Abstract

We have discovered that the bacterial toxins aerolysin and pertussis toxin share a common domain. This is surprising because the two toxins affect cells in very different ways. The common domain, which we call the APT domain, consists of two three-stranded antiparallel beta-sheets that come together and wrap around a central pair of helices. The APT domain shares a common fold with the C-type lectins and Link modules, and there appears to be a divergent relationship among the three families. One surface region of the APT domain is highly conserved, raising the possibility that the domains have a common function in both proteins. Mutation of one of the conserved surface residues in aerolysin, Tyr61, results in reduced receptor binding and activity, thus providing evidence that the APT domain may be involved in interaction with the toxin's receptor. Structural and biochemical evidence suggests that the APT domain contains a carbohydrate-binding site that can direct the toxins to their target cells.

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Selected References

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  1. Altwegg M., Geiss H. K. Aeromonas as a human pathogen. Crit Rev Microbiol. 1989;16(4):253–286. doi: 10.3109/10408418909105478. [DOI] [PubMed] [Google Scholar]
  2. Armstrong G. D., Howard L. A., Peppler M. S. Use of glycosyltransferases to restore pertussis toxin receptor activity to asialoagalactofetuin. J Biol Chem. 1988 Jun 25;263(18):8677–8684. [PubMed] [Google Scholar]
  3. Bairoch A., Bucher P., Hofmann K. The PROSITE database, its status in 1995. Nucleic Acids Res. 1996 Jan 1;24(1):189–196. doi: 10.1093/nar/24.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ballard J., Crabtree J., Roe B. A., Tweten R. K. The primary structure of Clostridium septicum alpha-toxin exhibits similarity with that of Aeromonas hydrophila aerolysin. Infect Immun. 1995 Jan;63(1):340–344. doi: 10.1128/iai.63.1.340-344.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barton G. J. ALSCRIPT: a tool to format multiple sequence alignments. Protein Eng. 1993 Jan;6(1):37–40. doi: 10.1093/protein/6.1.37. [DOI] [PubMed] [Google Scholar]
  6. Bertrand J. A., Pignol D., Bernard J. P., Verdier J. M., Dagorn J. C., Fontecilla-Camps J. C. Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J. 1996 Jun 3;15(11):2678–2684. [PMC free article] [PubMed] [Google Scholar]
  7. Brennan M. J., David J. L., Kenimer J. G., Manclark C. R. Lectin-like binding of pertussis toxin to a 165-kilodalton Chinese hamster ovary cell glycoprotein. J Biol Chem. 1988 Apr 5;263(10):4895–4899. [PubMed] [Google Scholar]
  8. Brissett N. C., Perkins S. J. The protein fold of the hyaluronate-binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C-type lectin superfamily. FEBS Lett. 1996 Jun 17;388(2-3):211–216. doi: 10.1016/0014-5793(96)00576-5. [DOI] [PubMed] [Google Scholar]
  9. Buckley J. T. Purification of cloned proaerolysin released by a low protease mutant of Aeromonas salmonicida. Biochem Cell Biol. 1990 Jan;68(1):221–224. doi: 10.1139/o90-029. [DOI] [PubMed] [Google Scholar]
  10. Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem. 1988 Jul 15;263(20):9557–9560. [PubMed] [Google Scholar]
  11. Fraser M. E., Chernaia M. M., Kozlov Y. V., James M. N. Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution. Nat Struct Biol. 1994 Jan;1(1):59–64. doi: 10.1038/nsb0194-59. [DOI] [PubMed] [Google Scholar]
  12. Green M. J., Buckley J. T. Site-directed mutagenesis of the hole-forming toxin aerolysin: studies on the roles of histidines in receptor binding and oligomerization of the monomer. Biochemistry. 1990 Feb 27;29(8):2177–2180. doi: 10.1021/bi00460a031. [DOI] [PubMed] [Google Scholar]
  13. Hardie K. R., Schulze A., Parker M. W., Buckley J. T. Vibrio spp. secrete proaerolysin as a folded dimer without the need for disulphide bond formation. Mol Microbiol. 1995 Sep;17(6):1035–1044. doi: 10.1111/j.1365-2958.1995.mmi_17061035.x. [DOI] [PubMed] [Google Scholar]
  14. Howard S. P., Buckley J. T. Membrane glycoprotein receptor and hole-forming properties of a cytolytic protein toxin. Biochemistry. 1982 Mar 30;21(7):1662–1667. doi: 10.1021/bi00536a029. [DOI] [PubMed] [Google Scholar]
  15. Jones T. A., Zou J. Y., Cowan S. W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. doi: 10.1107/s0108767390010224. [DOI] [PubMed] [Google Scholar]
  16. Kohda D., Morton C. J., Parkar A. A., Hatanaka H., Inagaki F. M., Campbell I. D., Day A. J. Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration. Cell. 1996 Sep 6;86(5):767–775. doi: 10.1016/s0092-8674(00)80151-8. [DOI] [PubMed] [Google Scholar]
  17. Loosmore S., Zealey G., Cockle S., Boux H., Chong P., Yacoob R., Klein M. Characterization of pertussis toxin analogs containing mutations in B-oligomer subunits. Infect Immun. 1993 Jun;61(6):2316–2324. doi: 10.1128/iai.61.6.2316-2324.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Merritt E. A., Sarfaty S., van den Akker F., L'Hoir C., Martial J. A., Hol W. G. Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide. Protein Sci. 1994 Feb;3(2):166–175. doi: 10.1002/pro.5560030202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Montecucco C., Tomasi M., Schiavo G., Rappuoli R. Hydrophobic photolabelling of pertussis toxin subunits interacting with lipids. FEBS Lett. 1986 Jan 6;194(2):301–304. doi: 10.1016/0014-5793(86)80105-3. [DOI] [PubMed] [Google Scholar]
  20. Murzin A. G., Brenner S. E., Hubbard T., Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. doi: 10.1006/jmbi.1995.0159. [DOI] [PubMed] [Google Scholar]
  21. Parker M. W., Buckley J. T., Postma J. P., Tucker A. D., Leonard K., Pattus F., Tsernoglou D. Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane-channel states. Nature. 1994 Jan 20;367(6460):292–295. doi: 10.1038/367292a0. [DOI] [PubMed] [Google Scholar]
  22. Parker M. W., van der Goot F. G., Buckley J. T. Aerolysin--the ins and outs of a model channel-forming toxin. Mol Microbiol. 1996 Jan;19(2):205–212. doi: 10.1046/j.1365-2958.1996.355887.x. [DOI] [PubMed] [Google Scholar]
  23. Pittman M. The concept of pertussis as a toxin-mediated disease. Pediatr Infect Dis. 1984 Sep-Oct;3(5):467–486. doi: 10.1097/00006454-198409000-00019. [DOI] [PubMed] [Google Scholar]
  24. Rozdzinski E., Jones T., Burnette W. N., Burroughs M., Tuomanen E. Antiinflammatory effects in experimental meningitis of prokaryotic peptides that mimic selectins. J Infect Dis. 1993 Dec;168(6):1422–1428. doi: 10.1093/infdis/168.6.1422. [DOI] [PubMed] [Google Scholar]
  25. Ruf A., Mennissier de Murcia J., de Murcia G., Schulz G. E. Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7481–7485. doi: 10.1073/pnas.93.15.7481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saukkonen K., Burnette W. N., Mar V. L., Masure H. R., Tuomanen E. I. Pertussis toxin has eukaryotic-like carbohydrate recognition domains. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):118–122. doi: 10.1073/pnas.89.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sixma T. K., Pronk S. E., Kalk K. H., Wartna E. S., van Zanten B. A., Witholt B., Hol W. G. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature. 1991 May 30;351(6325):371–377. doi: 10.1038/351371a0. [DOI] [PubMed] [Google Scholar]
  28. Stein P. E., Boodhoo A., Armstrong G. D., Cockle S. A., Klein M. H., Read R. J. The crystal structure of pertussis toxin. Structure. 1994 Jan 15;2(1):45–57. doi: 10.1016/s0969-2126(00)00007-1. [DOI] [PubMed] [Google Scholar]
  29. Stein P. E., Boodhoo A., Armstrong G. D., Heerze L. D., Cockle S. A., Klein M. H., Read R. J. Structure of a pertussis toxin-sugar complex as a model for receptor binding. Nat Struct Biol. 1994 Sep;1(9):591–596. doi: 10.1038/nsb0994-591. [DOI] [PubMed] [Google Scholar]
  30. Stein P. E., Boodhoo A., Tyrrell G. J., Brunton J. L., Read R. J. Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli. Nature. 1992 Feb 20;355(6362):748–750. doi: 10.1038/355748a0. [DOI] [PubMed] [Google Scholar]
  31. Tallett A., Seabrook R. N., Irons L. I., Robinson A., Van Heyningen S., Atkinson T. Localisation of a receptor-recognition domain on the S3 subunit of pertussis toxin by peptide mapping. Eur J Biochem. 1993 Feb 1;211(3):743–748. doi: 10.1111/j.1432-1033.1993.tb17604.x. [DOI] [PubMed] [Google Scholar]
  32. Weis W. I., Drickamer K., Hendrickson W. A. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature. 1992 Nov 12;360(6400):127–134. doi: 10.1038/360127a0. [DOI] [PubMed] [Google Scholar]
  33. Weis W. I., Kahn R., Fourme R., Drickamer K., Hendrickson W. A. Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science. 1991 Dec 13;254(5038):1608–1615. doi: 10.1126/science.1721241. [DOI] [PubMed] [Google Scholar]
  34. Witvliet M. H., Burns D. L., Brennan M. J., Poolman J. T., Manclark C. R. Binding of pertussis toxin to eucaryotic cells and glycoproteins. Infect Immun. 1989 Nov;57(11):3324–3330. doi: 10.1128/iai.57.11.3324-3330.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zhang R. G., Scott D. L., Westbrook M. L., Nance S., Spangler B. D., Shipley G. G., Westbrook E. M. The three-dimensional crystal structure of cholera toxin. J Mol Biol. 1995 Aug 25;251(4):563–573. doi: 10.1006/jmbi.1995.0456. [DOI] [PubMed] [Google Scholar]

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