Advertisement

European Biophysics Journal

, Volume 33, Issue 3, pp 233–237 | Cite as

Analysis of peptaibol sequence composition: implications for in vivo synthesis and channel formation

  • L. Whitmore
  • B. A. Wallace
Article

Abstract

The sequence entries in the Peptaibol Database were analysed to provide information on compositional features of this unusual family of peptides. The non-standard amino acid α-aminoisobutyric acid represents almost 40% of the residues in all the known sequences. Glutamine is the only significant polar residue in peptaibols, and the position and number of these residues appear to be related to their functional properties as ion channels. Aromatic residues are clustered at the termini, which may contribute to stabilization of the peptide vertically within the bilayer. The peptide chain length is strongly weighted towards the longer members of the family (16–20 residues) and likely to be an important feature in their mode of action as transmembrane permeabilizers. The significant skewing towards even numbers of residues and the bias in pairwise distributions of amino acids have implications for the nature of the in vivo synthesis of these peptides via large non-ribosomal protein complexes.

Keywords

Bioinformatics Database Ion channels Non-ribosomal synthesis Peptide structure 

Notes

Acknowledgements

This work was supported, in part, by BBSRC grant B13586 to B.A.W.

References

  1. Anders R, Ohlenschlager O, Soskic V, Wenschuh H, Heise B, Brown LR (2000) The NMR solution structure of the ion channel peptaibol chrysospermin C bound to dodecylphosphocholine micelles. Eur J Biochem 267:1784–1794CrossRefPubMedGoogle Scholar
  2. Balashova TA, Shenkarev, ZO, Tagaev AA, Ovchinnikova TV, Raap J, Arseniev AS (2000) NMR structure of the channel-former zervamicin IIB in isotropic solvents. FEBS Lett 466:333–336CrossRefPubMedGoogle Scholar
  3. Boheim G (1974) Statistical analysis of alamethicin channels in black lipid membranes. J Membr Biol 19:277–303PubMedGoogle Scholar
  4. Chugh JK, Wallace BA (2001) Peptaibols: models for ion channels. Biochem Soc Trans 29:565–570PubMedGoogle Scholar
  5. Chugh JK, Brückner H, Wallace BA. (2002) Model for a helical bundle channel based on the high resolution crystal structure of trichotoxin_A50E. Biochemistry 41:12934–12941CrossRefPubMedGoogle Scholar
  6. Esposito G, Carver JA, Boyd J, Campbell ID (1987) High resolution 1H NMR study of the solution structure of alamethicin. Biochemistry 26:1043–1050PubMedGoogle Scholar
  7. Fox RO Jr, Richards FM (1982) A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5 Å resolution. Nature 300:325–330PubMedGoogle Scholar
  8. Franklin JC, Ellena JF, Jayasinghe S, Kelsh LP, Cafiso DS (1994) Structure of micelle-associated alamethicin from 1H NMR: evidence for conformational heterogeneity in a voltage-gated peptide. Biochemistry 33:4036–4045PubMedGoogle Scholar
  9. Galbraith TP, Harris R, Driscoll PC, Wallace BA (2003) Solution NMR studies of antiamoebin, a membrane channel-forming polypeptide. Biophys J 84:185–194PubMedGoogle Scholar
  10. Karle IL, Flippen-Anderson JL, Agarwalla S, Balaram P (1991) Crystal structure of [leu1]-zervamicin, a membrane ion-channel peptide: implications for gating mechanisms. Proc Natl Acad Sci USA 88:5307–5311PubMedGoogle Scholar
  11. Karle IL, Perozzo MA, Mishra VK, Balaram P (1998) Crystal structure of the channel-forming polypeptide antiamoebin in a membrane-mimetic environment. Proc Natl Acad Sci USA 95:5501–5504CrossRefPubMedGoogle Scholar
  12. Nagaoka Y, Iida A, Kambara T, Asami K, Fujita T (1996) Role of 61n (7) in the ion channel forming, properties of the peptaibol trichosporin-B-VIa. Chem Commun 9:1079–1080Google Scholar
  13. Prasad BVV, Balaram P (1984) The stereochemistry of peptides containing alpha-aminoisobutyric acid. CRC Crit Rev Biochem 16:307–348PubMedGoogle Scholar
  14. Sansom MSP (1993) Alamethicin and related peptaibols: model ion channels. Eur Biophys J 22:105–124PubMedGoogle Scholar
  15. Schiffer M, Chang CH, Stevens FJ (1992) The functions of tryptophan residues in membrane proteins. Protein Eng 5:213–214PubMedGoogle Scholar
  16. Shenkarev ZO, Balashova TA, Efremov RG, Yakimenko ZA, Ovchinnikova TV, Raap J, Arseniev AS (2002) Spatial structure of zervamicin IIB bound to DPC micelles: implications for voltage-gating. Biophys J 82:762–771PubMedGoogle Scholar
  17. Snook CF, Woolley, GA, Oliva G, Pattabhi V, Wood SP, Blundell TL, Wallace BA (1998) The structure and function of antiamoebin I, a proline-rich membrane-active polypeptide. Structure 6:783–792PubMedGoogle Scholar
  18. Toniolo C, Benedetti E (1991) The polypeptide 310 helix. Trends Biochem Sci 16:350–353CrossRefPubMedGoogle Scholar
  19. Toniolo C, Peggion E, Crisma M, Formaggio F, Shui XQ, Eggleston DS (1994) Structure determination of racemic trichogin-A-IV using centrosymmetric crystals. Nat Struct Biol 1:908–914PubMedGoogle Scholar
  20. Toniolo C, Crisma M, Formaggio F, Peggion C, Monaco V, Goulard C, Rebuffat S, Bodo B (1996) Effect of N-alpha-acyl chain length on the membrane-modifying properties of synthetic analogs of the lipopeptaibol trichogin_GA IV. J Am Chem Soc 118:4952–4958CrossRefGoogle Scholar
  21. Wade D, Englund J (2002) Synthetic antibiotic peptides database. Protein Pept Lett 9:53–57PubMedGoogle Scholar
  22. Wallace BA (2000) Common features in gramicidin and other ion channels. Bioessays 22:227–234PubMedGoogle Scholar
  23. Wallace BA, Janes RW (1999) Tryptophans in membrane proteins: X-ray crystallographic analyses. Adv Exp Med Biol 467:789–799PubMedGoogle Scholar
  24. Whitmore L, Chugh JK, Snook CF, Wallace BA (2003) The peptaibol database: a sequence and structure resource. J Pept Sci (in press)Google Scholar
  25. Wiest A, Grzegorski D, Xu BW, Goulard C, Rebuffat S, Ebbole DJ, Bodo B, Kenerley C (2002) Identification of peptaibols from Trichoderma virens and cloning of a peptaibol synthetase. J Biol Chem 277:20862–20868CrossRefPubMedGoogle Scholar

Copyright information

© EBSA 2003

Authors and Affiliations

  1. 1.Department of CrystallographyBirkbeck College, University of LondonLondonUK

Personalised recommendations