Self-Assembly of Fused Homo-Oligomers to Create Nanotubes

  • Idit Buch
  • Chung-Jung Tsai
  • Haim J. Wolfson
  • Ruth Nussinov
Part of the Methods in Molecular Biology™ book series (MIMB, volume 474)

Summary

The formation of a nanostructure by self-assembly of a peptide or protein building block depends on the ability of the building block to spontaneously assemble into an ordered structure. We first describe a protocol of fusing homo-oligomer proteins with a given three-dimensional (3D) structure to create new building blocks. According to this protocol, a single monomer A that self-assembles with identical copies to create an oligomer A 1 is covalently linked, through a short linker L, to another monomer B that self-assembles with identical copies to create the oligomer B j . The result is a fused monomer A - L - B, which has the ability to self-assemble into a nanostructure (A - L - B) k . We control the self-assembly process of A - L - B by mapping the fused building block onto a planar sheet and wrapping the sheet around a cylinder with the target's dimensions. Finally, we validate the created nanotubes by an optimization procedure. We provide examples of two nanotubes in atomistic model details. One of these has experimental data. In principal, such a protocol should enable the creation of a wide variety of potentially useful protein-based nanotubes with control over their physical and chemical properties.

Key Words

Building block (BB) homo-oligomers oligomerization domain nanotube self-assembly symmetry unit-cell 

Notes

Acknowledgments

We thank Nurit Haspel and Dan Fishelovitch for their help and support. The computation times were provided by the National Cancer Institutes Frederick Advanced Biomedical Supercomputing Center and by the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health (NIH), Bethesda, Maryland (http://biowulf.nih.gov). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organization does not imply endorsement by the U.S. government.

References

  1. 1.
    Ferrari M. (2005) Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161–171.CrossRefGoogle Scholar
  2. 2.
    Ferrari M. (2005) Nanovector therapeutics. Curr. Opin. Chem. Biol. 9, 343–346.CrossRefGoogle Scholar
  3. 3.
    Ma B, Nussinov R. (2002) Stabilities and conformations of Alzheimers beta-amyloid peptide oligomers (Abeta 16–22, Abeta 16–35, and Abeta 10–35): sequence effects. Proc. Natl. Acad. Sci. U. S. A. 99, 14126–14131.CrossRefGoogle Scholar
  4. 4.
    Zhang S. (2003) Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 21, 1171–1178.CrossRefGoogle Scholar
  5. 5.
    Tsai CJ, Zheng J, Aleman C, Nussinov R. (2006) Structure by design: from single proteins and their building blocks to nanostructures. Trends Biotechnol. 24, 449–454.CrossRefGoogle Scholar
  6. 6.
    Haspel N, Zanuy D, Aleman C, Wolfson H, Nussinov R. (2006) De novo tubular nanostructure design based on self-assembly of beta-helical protein motifs. Structure 14, 1137–1148.CrossRefGoogle Scholar
  7. 7.
    Yemini M, Reches M, Rishpon J, Gazit E. (2005) Novel electrochemical biosensing platform using self-assembled peptide nanotubes. Nano. Lett. 5, 183–186.CrossRefGoogle Scholar
  8. 8.
    Beniash E, Hartgerink JD, Storrie H, Stendahl JC, Stupp SI. (2005) Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomater. 1, 387–397.CrossRefGoogle Scholar
  9. 9.
    Horne WS, Stout CD, Ghadiri MR. (2003) (A heterocyclic peptide nanotube. J. Am. Chem. Soc. 125, 9372–9376.CrossRefGoogle Scholar
  10. 10.
    Kohli RM, Walsh CT, Burkart MD. (2002) Biomimetic synthesis and optimization of cyclic peptide antibiotics. Nature 418, 658–661.CrossRefGoogle Scholar
  11. 11.
    Frank R. (2002) The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports—principles and applications. J. Immunol. Methods 267, 13–26.CrossRefGoogle Scholar
  12. 12.
    Padilla JE, Colovos C, Yeates TO. (2001) Nanohedra: using symmetry to design self assembling protein cages, layers, crystals, and filaments. Proc. Natl. Acad. Sci. U. S. A. 98, 2217–2221.CrossRefGoogle Scholar
  13. 13.
    Tsai CJ, Zheng J, Nussinov R. (2006) Designing a nanotube using naturally occurring protein building blocks. PLoS Comput. Biol. 2, e42.Google Scholar
  14. 14.
    Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. (1983) CHARMM—a program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4, 187–217.CrossRefGoogle Scholar
  15. 15.
    Berman HM, Westbrook J, Feng Z, et al. (2000) The Protein Data Bank. Nucleic Acids Res. 28, 235–242.CrossRefGoogle Scholar
  16. 16.
    Phillips JC, Braun R, Wang W, et al. (2005) Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802.CrossRefGoogle Scholar
  17. 17.
    Shatsky M, Nussinov R, Wolfson HJ. (2004) A method for simultaneous alignment of multiple protein structures. Proteins 56, 143–156.CrossRefGoogle Scholar
  18. 18.
    Pearson WR, Lipman DJ. (1988) Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. U. S. A. 85, 2444–2448.CrossRefGoogle Scholar
  19. 19.
    Smith TF, Waterman MS. (1981) Identification of common molecular subsequences. J. Mol. Biol. 147, 195–197.CrossRefGoogle Scholar
  20. 20.
    Akey DL, Malashkevich VN, Kim PS. (2001) Buried polar residues in coiled-coil interfaces. Biochemistry 40, 6352–6360.CrossRefGoogle Scholar
  21. 21.
    Davison TS, Nie X, Ma W, et al. (2001) Structure and functionality of a designed p53 dimer. J. Mol. Biol. 307, 605–617.CrossRefGoogle Scholar
  22. 22.
    Thoden JB, Firestine SM, Benkovic SJ, Holden HM. (2002) PurT-encoded glyc-inamide ribonucleotide transformylase. Accommodation of adenosine nucleotide analogs within the active site. J. Biol. Chem. 277, 23898–23908.CrossRefGoogle Scholar
  23. 23.
    Li S, Hill CP, Sundquist WI, Finch JT. (2000) Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407, 409–413.CrossRefGoogle Scholar
  24. 24.
    Monaco-Malbet S, Berthet-Colominas C, Novelli A, et al. (2000). Mutual confor-mational adaptations in antigen and antibody upon complex formation between an Fab and HIV-1 capsid protein p24. Structure 8, 1069–1077.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Idit Buch
    • 1
  • Chung-Jung Tsai
    • 2
  • Haim J. Wolfson
    • 3
  • Ruth Nussinov
    • 4
  1. 1.Department of Human Genetics, Sackler Institute of Molecular Medicine, Sackler Faculty of MedicineTel Aviv UniversityIsrael
  2. 2.SAIC-Frederick Inc., Center for Cancer Research Nanobiology ProgramNCI-FrederickFrederick
  3. 3.School of Computer ScienceTel Aviv UniversityIsrael
  4. 4.Center for Cancer Research Nanobiology Program SAIC-Frederick, National Cancer Institute. Department of Human GeneticsMedical School, Tel Aviv UniversityIsrael

Personalised recommendations