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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ferrari M. (2005) Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161–171.
Ferrari M. (2005) Nanovector therapeutics. Curr. Opin. Chem. Biol. 9, 343–346.
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.
Zhang S. (2003) Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 21, 1171–1178.
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.
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.
Yemini M, Reches M, Rishpon J, Gazit E. (2005) Novel electrochemical biosensing platform using self-assembled peptide nanotubes. Nano. Lett. 5, 183–186.
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.
Horne WS, Stout CD, Ghadiri MR. (2003) (A heterocyclic peptide nanotube. J. Am. Chem. Soc. 125, 9372–9376.
Kohli RM, Walsh CT, Burkart MD. (2002) Biomimetic synthesis and optimization of cyclic peptide antibiotics. Nature 418, 658–661.
Frank R. (2002) The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports—principles and applications. J. Immunol. Methods 267, 13–26.
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.
Tsai CJ, Zheng J, Nussinov R. (2006) Designing a nanotube using naturally occurring protein building blocks. PLoS Comput. Biol. 2, e42.
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.
Berman HM, Westbrook J, Feng Z, et al. (2000) The Protein Data Bank. Nucleic Acids Res. 28, 235–242.
Phillips JC, Braun R, Wang W, et al. (2005) Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802.
Shatsky M, Nussinov R, Wolfson HJ. (2004) A method for simultaneous alignment of multiple protein structures. Proteins 56, 143–156.
Pearson WR, Lipman DJ. (1988) Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. U. S. A. 85, 2444–2448.
Smith TF, Waterman MS. (1981) Identification of common molecular subsequences. J. Mol. Biol. 147, 195–197.
Akey DL, Malashkevich VN, Kim PS. (2001) Buried polar residues in coiled-coil interfaces. Biochemistry 40, 6352–6360.
Davison TS, Nie X, Ma W, et al. (2001) Structure and functionality of a designed p53 dimer. J. Mol. Biol. 307, 605–617.
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.
Li S, Hill CP, Sundquist WI, Finch JT. (2000) Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407, 409–413.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science + Business Media, LLC
About this protocol
Cite this protocol
Buch, I., Tsai, CJ., Wolfson, H.J., Nussinov, R. (2008). Self-Assembly of Fused Homo-Oligomers to Create Nanotubes. In: Gazit, E., Nussinov, R. (eds) Nanostructure Design. Methods in Molecular Biology™, vol 474. Humana Press. https://doi.org/10.1007/978-1-59745-480-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-59745-480-3_8
Publisher Name: Humana Press
Print ISBN: 978-1-934115-35-0
Online ISBN: 978-1-59745-480-3
eBook Packages: Springer Protocols