The Leucine Zipper as a Building Block for Self-Assembled Protein Fibers

  • Maxim G. Ryadnov
  • David Papapostolou
  • Derek N. Woolfson
Part of the Methods in Molecular Biology™ book series (MIMB, volume 474)


Nanostructured materials are receiving increased attention from both academia and industry. For example, the fundamental understanding of fiber formation by peptides and proteins both is of interest in itself and may lead to a range of applications. A key idea here is that the folding and subsequent supramolecular assembly of the monomers can be programmed within polypeptide chains. Thus, with an understanding of so-called sequence-to-structure relationships for these peptide assemblies, it may be possible to design novel nanostructures from the bottom up that exhibit properties determined by, but not characteristic of, their component building blocks. In this respect, the α-helical leucine zipper presents an excellent place to start in the rational design of ordered nanostructures that span several length scales. Indeed, such systems have been put forward and developed to different degrees. Despite their apparent diversity, they employ similar assembly routes that can be compiled into one basic methodology. This chapter gives examples and provides methods of what can be achieved through leucine zipper-based assembly of fibrous structures.

Key Words:

Fibers α-helical leucine zipper hierarchical self-assembly nanostructures peptide design supramolecular chemistry 


  1. 1.
    Zhang S. (2003) Fabrication of novel biomaterials through molecular self- assembly. Nat. Biotechnol. 21, 1171–1178.CrossRefGoogle Scholar
  2. 2.
    Ryadnov MG, Woolfson DN. (2007) Self-assembling nanostructures from coiled coil peptides. In: Mirkin CA, Niemeyer CM, eds. Nanobiotechnology II. Weinheim: Wiley-VCH; pp. 17–38.Google Scholar
  3. 3.
    Woolfson DN, Ryadnov MG. (2006) Peptide-based fibrous biomaterials: some things old, new and borrowed. Curr. Opin. Chem. Biol. 10, 559–567.CrossRefGoogle Scholar
  4. 4.
    Whitesides GM, Boncheva M. (2002) Supramolecular chemistry and self- assembly special feature: beyond molecules: self-assembly of mesoscopic and macroscopic components. Proc. Natl. Acad. Sci. U. S. A. 99, 4769–4774.CrossRefGoogle Scholar
  5. 5.
    Fairman R, Akerfeldt KS. (2005) Peptides as novel smart materials. Curr. Opin. Struct. Biol. 15, 453–463.CrossRefGoogle Scholar
  6. 6.
    Lupas AN, Gruber M. (2005) The structure of alpha-helical coiled coils. In: Parry DAD, Squire JM, eds. Advances in Protein Chemistry, Vol. 70. New York: Academic Press; pp. 37–38.Google Scholar
  7. 7.
    Burkhard P, Stetefeld J, Strelkov S V. (2001) Coiled coils: a highly versatile protein folding motif. Trends Cell Biol. 11, 82–88.CrossRefGoogle Scholar
  8. 8.
    Woolfson DN. (2005) The design of coiled-coil structures and assemblies. In: Parry DAD, Squire JM, eds. Advances in Protein Chemistry, Vol. 70. New York: Academic Press; pp. 79–112.Google Scholar
  9. 9.
    Raman S, Machaidze G, Lustig A, Aebi U, Burkhard P. (2006) Structure-based design of peptides that self-assemble into regular polyhedral nanoparticles. Nanomed. Nanotechnol. Biol. Med. 2, 95–102.CrossRefGoogle Scholar
  10. 10.
    Ryadnov MG. (2007) A self-assembling peptide polynanoreactor. Angew. Chem. Int. Ed. 46, 969–972.CrossRefGoogle Scholar
  11. 11.
    Ryadnov MG, Ceyhan B, Niemeyer CM, Woolfson D. N. (2003) “Belt and braces”: a peptide-based linker system of de novo design. J. Am. Chem. Soc. 125, 9388–9394.CrossRefGoogle Scholar
  12. 12.
    Wagner DE, Phillips CL, Ali WM, et al. (2005) Toward the development of peptide nanofilaments and nanoropes as smart materials. Proc. Natl. Acad. Sci. U. S. A. 102, 12656–12661.CrossRefGoogle Scholar
  13. 13.
    Ryadnov MG, Woolfson DN. (2003) Engineering the morphology of a self-assembling protein fibre. Nat. Mater. 2, 329–332.CrossRefGoogle Scholar
  14. 14.
    Ryadnov MG, Woolfson DN. (2003) Introducing branches into a self-assembling peptide fiber. Angew. Chem. Int. Ed. 42, 3021–3023.CrossRefGoogle Scholar
  15. 15.
    Ryadnov MG, Woolfson DN. (2005) MaP peptides: programming the self-assembly of peptide-based mesoscopic matrices. J. Am. Chem. Soc. 127, 12407–12415.CrossRefGoogle Scholar
  16. 16.
    Ryadnov MG, Woolfson DN. (2004) Fiber recruiting peptides: noncovalent decoration of an engineered protein scaffold. J. Am. Chem. Soc. 126, 7454–7455.CrossRefGoogle Scholar
  17. 17.
    Smith AM, Acquah SFA, Bone N, et al. (2005) Polar assembly in a designed protein fiber. Angew. Chem. Int. Ed. 44, 325–328.CrossRefGoogle Scholar
  18. 18.
    Zimenkov Y, Dublin SN, Ni R, et al. (2006) Rational design of a reversible pH-responsive switch for peptide self-assembly. J. Am. Chem. Soc. 128, 6770–6771.CrossRefGoogle Scholar
  19. 19.
    Pandya MJ, Spooner GM, Sunde M, Thorpe JR, Rodger A, Woolfson DN. (2000) Sticky-end assembly of a designed peptide fiber provides insight into protein fibrillogenesis. Biochemistry 39, 8728–8734.CrossRefGoogle Scholar
  20. 20.
    Zhang S. (2003) Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 21, 1171–1178.CrossRefGoogle Scholar
  21. 21.
    Whitesides GM. (2006) The origins and the future of microfluidics. Nature 442, 368–373.CrossRefGoogle Scholar
  22. 22.
    Cerasoli E, Sharpe BK, Woolfson DN. (2005) ZiCo: a peptide designed to switch folded state upon binding zinc. J. Am. Chem. Soc. 127, 15008–15009.CrossRefGoogle Scholar
  23. 23.
    Wilken J, Kent SBH. (1998) Chemical protein synthesis. Curr. Opin. Biotechnol. 9, 412–426.CrossRefGoogle Scholar
  24. 24.
    Nilsson BL, Soellner MB, Raines RT. (2005) Chemical synthesis of proteins. Annu. Rev. Biophys. Biomol. Struct. 34, 91–118.CrossRefGoogle Scholar
  25. 25.
    Zhou M, Bentley D, Ghosh I. (2004) Helical supramolecules and fibers utilizing leucine zipper-displaying dendrimers. J. Am. Chem. Soc. 126, 734–735.CrossRefGoogle Scholar
  26. 26.
    Severin K, Lee DH, Kennan AJ, Ghadiri MR. (1997) A synthetic peptide ligase. Nature 389, 706–709.CrossRefGoogle Scholar
  27. 27.
    Herrmann H, Aebi U. (2004) Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu. Rev. Biochem. 73, 749–789.CrossRefGoogle Scholar
  28. 28.
    Potekhin SA, Melnik TN, Popov V, et al. (2001) De novo design of fibrils made of short alpha-helical coiled coil peptides. Chem. Biol. 8, 1025–1032.CrossRefGoogle Scholar
  29. 29.
    Smith AM, Banwell EF, Edwards WR, Pandya MJ, Woolfson DN. (2006) Engineering increased stability into self-assembled protein fibers. Adv. Funct. Mater. 16, 1022–1030.CrossRefGoogle Scholar
  30. 30.
    Zimenkov Y, Conticello VP, Guo L, Thiyagarajan P. (2004) Rational design of a nanoscale helical scaffold derived from self-assembly of a dimeric coiled coil motif. Tetrahedron 60, 7237–7246.CrossRefGoogle Scholar
  31. 31.
    Aletras A, Barlos K, Gatos D, Koutsogianni S, Mamos P. (1995) Preparation of the very acid-sensitive Fmoc-Lys(Mtt)-OH. Application in the synthesis of side-chain to side-chain cyclic peptides and oligolysine cores suitable for the solid-phase assembly of MAPs and TASPs. Int. J. Pept. Protein Res. 45, 488–496.CrossRefGoogle Scholar
  32. 32.
    Kates SA, Daniels SB. (1993) Automated allyl cleavage for continuous-flow synthesis of cyclic and branched peptides. Anal. Biochem. 212, 303–310.CrossRefGoogle Scholar
  33. 33.
    Papapostolou D, Smith AM, Atkins EDT, et al. (2007) Engineering nanoscale order into a designed protein fiber. Proc. Natl. Acad. Sci. U. S. A. 104, 10853–10858.CrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Maxim G. Ryadnov
    • 1
  • David Papapostolou
    • 1
  • Derek N. Woolfson
    • 1
    • 2
  1. 1.School of ChemistryUniversity of BristolBristolUK
  2. 2.Department of Biochemistry, School of Medical SciencesUniversity WalkBristolUK

Personalised recommendations