Skip to main content
SpringerLink
Log in

De Novo Design of Peptide Scaffolds as Novel Preorganized Ligands for Metal-Ion Coordination

  • Protocol
  • First Online:
Protein Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1216))

Abstract

This chapter describes how de novo designed peptides can be used as novel preorganized ligands for metal ion coordination. The focus is on the design of peptides which are programmed to spontaneously self-assemble into α-helical coiled coils in aqueous solution, and how metal ion binding sites can be engineered onto and into these structures. In addition to describing the various design principles, some key examples are covered illustrating the success of this approach, including a more detailed example in the case study.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Venkatraman J, Naganagowda GA, Sudha R, Balaram P (2001) De novo design of a five-stranded beta-sheet anchoring a metal-ion binding site. Chem Commun 24:2660–2661

    Article  Google Scholar 

  2. Yang W, Jones LM, Isley L, Ye Y, Lee H-W, Wilkins A et al (2003) Rational design of a calcium-binding protein. J Am Chem Soc 125:6165–6171

    Article  PubMed  CAS  Google Scholar 

  3. Platt G, Chung CW, Searle MS (2001) Design of histidine-Zn2+ binding sites within a beta-hairpin peptide: enhancement of beta-sheet stability through metal complexation. Chem Commun 13:1162–1163

    Article  Google Scholar 

  4. Bonomo RP, Casella L, De Gioia L, Molinari H, Impellizzeri G, Jordan T et al (1997) Metal ion and proton stabilisation of turn motif in the synthetic octapeptide histidyltris(glycylhistidyl) glycine. J Chem Soc Dalton Trans 14:2387–2389

    Article  Google Scholar 

  5. Krizek BA, Merkle DL, Berg JM (1993) Ligand variation and metal-ion binding specificity in zinc finger peptides. Inorg Chem 32:937–940

    Article  CAS  Google Scholar 

  6. Ende CWA, Meng HY, Ye M, Ye M, Pandey AK, Zondlo NJ (2010) Design of lanthanide fingers: compact lanthanide-binding metalloproteins. Chembiochem 11:1738–1747

    Article  Google Scholar 

  7. Apostolovic B, Danial M, Klok H-A (2010) Coiled coils: attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials. Chem Soc Rev 39:3541–3575

    Article  PubMed  CAS  Google Scholar 

  8. Woolfson DN (2005) The design of coiled-coil structures and assemblies. In: Parry D, Squire J (eds) Fibrous proteins: coiled-coils, collagen and elastomers, vol 70, 1st edn. Elsevier and Academic, Boston, MA, pp 79–112, Adv Protein Chem

    Google Scholar 

  9. Liu J, Yong W, Deng YQ, Kallenbach NR, Lu M (2004) Atomic structure of a tryptophan-zipper pentamer. Proc Natl Acad Sci U S A 101:16156–16161

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Liu J, Zheng Q, Deng Y, Kallenbach NR, Lu M (2006) Conformational transition between four and five-stranded phenylalanine zippers determined by a local packing interaction. J Mol Biol 361:168–179

    Article  PubMed  CAS  Google Scholar 

  11. Zhou NE, Kay CM, Hodges RS (1994) The role of interhelical ionic interactions in controlling protein-folding and stability—de novo designed synthetic 2-stranded alpha-helical coiled-coils. J Mol Biol 237:500–512

    Article  PubMed  CAS  Google Scholar 

  12. De Crescenzo G, Litowski JR, Hodges RS, O’Connor-McCourt MD (2003) Real-time monitoring of the interactions of two-stranded de novo designed coiled-coils: effect of chain length on the kinetic and thermodynamic constants of binding. Biochemistry 42:1754–1763

    Article  PubMed  Google Scholar 

  13. Su JY, Hodges RS, Kay CM (1994) Effect of chain-length on the formation and stability of synthetic alpha-helical coiled coils. Biochemistry 33:15501–15510

    Article  PubMed  CAS  Google Scholar 

  14. Pace CN, Scholtz JM (1998) A helix propensity scale based on experimental studies of peptides and proteins. Biophys J 75:422–427

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Strehlow KG, Robertson AD, Baldwin RL (1991) Proline for alanine substitutions in the C-peptide helix of ribonuclease-A. Biochemistry 30:5810–5814

    Article  PubMed  CAS  Google Scholar 

  16. Fletcher JM, Boyle AL, Bruning M, Bartlett GJ, Vincent TL, Zaccai NR et al (2012) A basis set of de novo coiled-coil peptide oligomers for rational protein design and synthetic biology. ACS Synth Biol 1:240–250

    Article  PubMed  CAS  Google Scholar 

  17. Mahmoud ZN, Gunnoo SB, Thomson AR, Fletcher JM, Woolfson DN (2011) Bioorthogonal dual functionalization of self-assembling peptide fibers. Biomaterials 32:3712–3720

    Article  PubMed  CAS  Google Scholar 

  18. Keating AE, Malashkevich VN, Tidor B, Kim PS (2001) Side-chain repacking calculations for predicting structures and stabilities of heterodimeric coiled coils. Proc Natl Acad Sci U S A 98:14825–14830

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Nautiyal S, Alber T (1999) Crystal structure of a designed, thermostable; heterotrimeric coiled coil. Protein Sci 8:84–90

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Holton J, Alber T (2004) Automated protein crystal structure determination using ELVES. Proc Natl Acad Sci U S A 101:1537–1542

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Gonzalez L, Plecs JJ, Alber T (1996) An engineered allosteric switch in leucine-zipper oligomerization. Nat Struct Biol 3:510–515

    Article  PubMed  CAS  Google Scholar 

  22. Kashiwada A, Hiroaki H, Kohda D, Nango M, Tanaka T (2000) Design of a heterotrimeric alpha-helical bundle by hydrophobic core engineering. J Am Chem Soc 122:212–215

    Article  CAS  Google Scholar 

  23. Walsh STR, Cheng H, Bryson JW, Roder H, DeGrado WF (1999) Solution structure and dynamics of a de novo designed three-helix bundle protein. Proc Natl Acad Sci U S A 96:5486–5491

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Baltzer L, Nilsson H, Nilsson J (2001) De novo design of proteins—what are the rules? Chem Rev 101:3153–3163

    Article  PubMed  CAS  Google Scholar 

  25. Chakraborty S, Kravitz JY, Thulstrup PW, Hemmingsen L, DeGrado WF, Pecoraro VL (2011) Design of a three-helix bundle capable of binding heavy metals in a triscysteine environment. Angew Chem Int Ed 50: 2049–2053

    Article  CAS  Google Scholar 

  26. Dokmanic I, Sikic M, Tomic S (2008) Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination. Acta Crystallogr D Biol Crystallogr 64:257–263

    Article  PubMed  CAS  Google Scholar 

  27. Tanaka T, Mizuno T, Fukui S, Hiroaki H, Oku J, Kanaori K et al (2004) Two-metal ion, Ni(II) and Cu(II), binding alpha-helical coiled coil peptide. J Am Chem Soc 126:14023–14028

    Article  PubMed  CAS  Google Scholar 

  28. Zastrow ML, Peacock AFA, Stuckey JA, Pecoraro VL (2012) Hydrolytic catalysis and structural stabilization in a designed metalloprotein. Nat Chem 4:118–123

    Article  CAS  Google Scholar 

  29. Bowman GD, Nodelman IM, Levy O, Li SL, Tian P, Zamb TJ et al (2000) Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site. J Mol Biol 304:861–871

    Article  PubMed  CAS  Google Scholar 

  30. Peacock AFA, Bullen GA, Gethings LA, Williams JP, Kriel FH, Coates J (2012) Gold-phosphine binding to de novo designed coiled coil peptides. J Inorg Biochem 117:298–305

    Article  PubMed  CAS  Google Scholar 

  31. Neupane KP, Pecoraro VL (2010) Probing a homoleptic PbS3 coordination environment in a designed peptide using Pb-207 NMR spectroscopy: implications for understanding the molecular basis of lead toxicity. Angew Chem Int Ed 49:8177–8180

    Article  CAS  Google Scholar 

  32. Peacock AFA, Iranzo O, Pecoraro VL (2009) Harnessing natures ability to control metal ion coordination geometry using de novo designed peptides. Dalton Trans 13:2271–2280

    Article  PubMed  Google Scholar 

  33. Peacock AFA, Pecoraro VL (2013) Natural and artificial proteins containing cadmium. In: Sigel A, Sigel H, Sigel RKO (eds) Cadmium: from toxicity to essentiality, vol 11, Metal ions in life sciences. Springer Science + Business Media B.V, Dordrecht, pp 303–307

    Google Scholar 

  34. Pecoraro VL, Peacock AFA, Iranzo O, Iranzo O, Luczkowski M (2009) Understanding the biological chemistry of mercury using a de novo protein design strategy. In: Long E, Baldwin M (eds) Advances in inorganic biochemistry: from synthetic models to cellular systems. ACS symposium series, vol 1012, pp 183–197

    Google Scholar 

  35. Cheng RP, Fisher SL, Imperiali B (1996) Metallopeptide design: tuning the metal cation affinities with unnatural amino acids and peptide secondary structure. J Am Chem Soc 118:11349–11356

    Article  CAS  Google Scholar 

  36. Petros AK, Shaner SE, Costello AL, Tierney DL, Gibney BR (2004) Comparison of cysteine and penicillamine ligands in a Co(II) maquette. Inorg Chem 43:4793–4795

    Article  PubMed  CAS  Google Scholar 

  37. Kashiwada A, Ishida K, Matsuda K (2007) Lanthanide ion-induced folding of de novo designed coiled-coil polypeptides. Bull Chem Soc Jpn 80:2203–2207

    Article  CAS  Google Scholar 

  38. Kohn WD, Kay CM, Sykes BD, Hodges RS (1998) Metal ion induced folding of a de novo designed coiled-coil peptide. J Am Chem Soc 120:1124–1132

    Article  CAS  Google Scholar 

  39. Dai Q, Dong M, Liu Z, Castellino FJ (2011) Ca2+-induced self-assembly in designed peptides with optimally spaced gamma-carboxyglutamic acid residues. J Inorg Biochem 105:52–57

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Torrado A, Imperiali B (1996) New synthetic amino acids for the design and synthesis of peptide-based metal ion sensors. J Org Chem 61(25):8940–8948

    Article  PubMed  CAS  Google Scholar 

  41. Rama G, Arda A, Marechal J-D, Gamba I, Ishida H, Jiménez-Barbero J et al (2012) Stereoselective formation of chiral metallopeptides. Chemistry 18:7030–7035

    Article  PubMed  CAS  Google Scholar 

  42. Barisic L, Rapic V, Metzler-Nolte N (2006) Incorporation of the unnatural organometallic amino acid 1′-aminoferrocene-1-carboxylic acid (Fca) into oligopeptides by a combination of Fmoc and Boc solid-phase synthetic methods. Eur J Inorg Chem 20:4019–4021

    Article  Google Scholar 

  43. Doerr AJ, McLendon GL (2004) Design, folding, and activities of metal-assembled coiled coil proteins. Inorg Chem 43:7916–7925

    Article  PubMed  CAS  Google Scholar 

  44. Schneider JP, Kelly JW (1995) Templates that induce alpha-helical, beta-sheet and loop conformations. Chem Rev 95:2169–2187

    Article  CAS  Google Scholar 

  45. Lieberman M, Sasaki T (1991) Iron(III) organizes a synthetic peptide into 3-helix bundles. J Am Chem Soc 113:1470–1471

    Article  CAS  Google Scholar 

  46. Ghadiri MR, Soares C, Choi C (1992) A convergent approach to protein design—metal-ion assisted spontaneous self-assembly of a poly peptide into a triple-helix bundle protein. J Am Chem Soc 114:825–831

    Article  CAS  Google Scholar 

  47. Mihara H, Nishino N, Hasegawa R, Fujimoto T, Usui S, Ishida H et al (1992) Design of a hybrid of 2 alpha helix peptides and ruthenium trisbipyridine complex for photoinduced electron-transfer system in bilayer-membrane. Chem Lett 9:1813–1816

    Article  Google Scholar 

  48. Samiappan M, Alasibi S, Cohen-Luria R, Shanzer A, Ashkenasy G (2012) Allosteric effects in coiled-coil proteins folding and lanthanide-ion Binding. Chem Comm 48:9577–9579

    Google Scholar 

  49. Tsurkan MV, Ogawa MY (2007) Metal-mediated peptide assembly: Use of metal coordination to change the oligomerization state of an alpha-helical coiled-coil. Inorg Chem 46:6849–6851

    Article  PubMed  CAS  Google Scholar 

  50. Kohn WD, Kay CM, Hodges RS (1998) Effects of lanthanide binding on the stability of de novo designed alpha-helical coiled-coils. J Pept Res 51:9–18

    Article  PubMed  CAS  Google Scholar 

  51. Choma CT, Lear JD, Nelson MJ, Dutton PL, Robertson DE, DeGrado WF (1994) Design of a heme-binding 4-helix bundle. J Am Chem Soc 116:856–865

    Article  CAS  Google Scholar 

  52. Robertson DE, Farid RS, Moser CC, Urbauer JL, Mulholland SE, Pidikiti R et al (1994) Design and synthesis of multi-heme proteins. Nature 368:425–431

    Article  PubMed  CAS  Google Scholar 

  53. Koder RL, Anderson JLR, Solomon LA, Reddy KS, Moser CC, Dutton LP (2009) Design and engineering of an O2 transport protein. Nature 458:305–309

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Chakraborty S, Touw D, Peacock AFA, Stuckey J, Pecoraro VL (2010) Structural comparisons of apo- and metalated three-stranded coiled coils clarify metal binding determinants in thiolate containing designed peptides. J Am Chem Soc 132:13240–13250

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  55. Dieckmann GR, McRorie DK, Tierney DL, Utschig LM, Singer CP, O'Halloran TV et al (1997) De novo design of mercury-binding two- and three-helical bundles. J Am Chem Soc 119:6195–6196

    Article  CAS  Google Scholar 

  56. Dieckmann GR, McRorie DK, Lear JD, Sharp KA, DeGrado WF, Pecoraro VL (1998) The role of protonation and metal chelation preferences in defining the properties of mercury-binding coiled coils. J Mol Biol 280:897–912

    Article  PubMed  CAS  Google Scholar 

  57. Iranzo O, Thulstrup PW, Ryu S-B, Hemmingsen L, Pecoraro VL (2007) The application of Hg-199 NMR and Hg-199 m perturbed angular correlation (PAC) spectroscopy to define the biological chemistry of Hg-II: a case study with designed two- and three-stranded coiled coils. Chemistry 13:9178–9190

    Article  PubMed  CAS  Google Scholar 

  58. Farrer BT, McClure CP, Penner-Hahn JE, Pecoraro VL (2000) Arsenic(III)-cysteine interactions stabilize three-helix bundles in aqueous solution. Inorg Chem 39:5422–5423

    Article  PubMed  CAS  Google Scholar 

  59. Touw DS, Nordman CE, Stuckey JA, Pecoraro VL (2007) Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils. Proc Natl Acad Sci U S A 104:11969–11974

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Matzapetakis M, Farrer BT, Weng TC, Hemmingsen L, Penner-Hahn JE, Pecoraro VL (2002) Comparison of the binding of cadmium(II), mercury(II), and arsenic(III) to the de novo designed peptides TRI L12C and TRI L16C. J Am Chem Soc 124:8042–8054

    Article  PubMed  CAS  Google Scholar 

  61. Lee KH, Matzapetakis M, Mitra S, Marsh EN, Pecoraro VL (2004) Control of metal coordination number in de novo designed peptides through subtle sequence modifications. J Am Chem Soc 126:9178–9179

    Article  PubMed  CAS  Google Scholar 

  62. Lee KH, Cabello C, Hemmingsen L, Marsh EN, Pecoraro VL (2006) Using nonnatural amino acids to control metal-coordination number in three-stranded coiled coils. Angew Chem Int Ed 45:2864–2868

    Article  CAS  Google Scholar 

  63. Peacock AFA, Hemmingsen L, Pecoraro VL (2008) Using diastereopeptides to control metal ion coordination in proteins. Proc Natl Acad Sci U S A 105:16566–16571

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  64. Ghosh D, Pecoraro VL (2004) Understanding metalloprotein folding using a de novo design strategy. Inorg Chem 43:7902–7915

    Article  PubMed  CAS  Google Scholar 

  65. Lovejoy B, Choe S, Cascio D, McRorie DK, DeGrado WF, Eisenberg D (1993) Crystal-structure of a synthetic triple-stranded alpha-helical bundle. Science 259:1288–1293

    Article  PubMed  CAS  Google Scholar 

  66. Peacock AFA, Stuckey JA, Pecoraro VL (2009) Switching the chirality of the metal environment alters the coordination mode in designed peptides. Angew Chem Int Ed 48:7371–7374

    Article  CAS  Google Scholar 

  67. Mittl PRE, Deillon C, Sargent D, Liu N, Klauser S, Thomas RM et al (2000) The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure. Proc Natl Acad Sci U S A 97:2562–2566

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  68. Harbury PB, Kim PS, Alber T (1994) Crystal-structure of an isoleucine-zipper trimer. Nature 371:80–83

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

AFAP and AJG thank the School of Chemistry at the University of Birmingham and the EPSRC (EP/J014672-1) for financial support.

Author information

Authors and Affiliations

  1. School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Aimee J. Gamble & Anna F. A. Peacock

Authors
  1. Aimee J. Gamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna F. A. Peacock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna F. A. Peacock .

Editor information

Editors and Affiliations

  1. Department of Chemistry, University of Basel, Switzerland

    Valentin Köhler

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Gamble, A.J., Peacock, A.F.A. (2014). De Novo Design of Peptide Scaffolds as Novel Preorganized Ligands for Metal-Ion Coordination. In: Köhler, V. (eds) Protein Design. Methods in Molecular Biology, vol 1216. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1486-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1486-9_11

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1485-2

  • Online ISBN: 978-1-4939-1486-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation