1 Citation (Scopus)

Abstract

Three-dimensional (3D) cages are one of the most important targets for nanotechnology. Both proteins and DNA have been used as building blocks to create tunable nanoscale cages for a wide range of applications, but each molecular type has its own limitations. Here, we report a cage constructed from both protein and DNA building blocks through the use of covalent protein-DNA conjugates. We modified a homotrimeric protein (KDPG aldolase) with three identical single-stranded DNA handles by functionalizing a reactive cysteine residue introduced via site-directed mutagenesis. This protein-DNA building block was coassembled with a triangular DNA structure bearing three complementary arms to the handles, resulting in tetrahedral cages comprising six DNA sides capped by the protein trimer. The dimensions of the cage could be tuned through the number of turns per DNA arm (3 turns â- 10 nm, 4 turns â- 14 nm), and the hybrid structures were purified and characterized to confirm the three-dimensional structure. Cages were also modified with DNA using click chemistry and using aldolase trimers bearing the noncanonical amino acid 4-azidophenylalanine, demonstrating the generality of the method. Our approach will allow for the construction of nanomaterials that possess the advantages of both protein and DNA nanotechnology and find applications in fields such as targeted delivery, structural biology, biomedicine, and catalytic materials.

Original languageEnglish (US)
Pages (from-to)3545-3554
Number of pages10
JournalACS Nano
Volume13
Issue number3
DOIs
StatePublished - Mar 26 2019

Fingerprint

assembling
DNA
deoxyribonucleic acid
proteins
Proteins
Bearings (structural)
aldolase
phospho-2-keto-3-deoxy-gluconate aldolase
Nanotechnology
nanotechnology
trimers
Mutagenesis
Fructose-Bisphosphate Aldolase
mutagenesis
Single-Stranded DNA
hybrid structures
cysteine
Nanostructured materials
biology
Cysteine

Keywords

  • 3D nanocages
  • aldolase trimer
  • DNA nanotechnology
  • DNprotein bioconjugation
  • DNprotein hybrids

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Xu, Y., Jiang, S., Simmons, C. R., Narayanan, R. P., Zhang, F., Aziz, A. M., ... Stephanopoulos, N. (2019). Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks. ACS Nano, 13(3), 3545-3554. https://doi.org/10.1021/acsnano.8b09798

Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks. / Xu, Yang; Jiang, Shuoxing; Simmons, Chad R.; Narayanan, Raghu Pradeep; Zhang, Fei; Aziz, Ann Marie; Yan, Hao; Stephanopoulos, Nicholas.

In: ACS Nano, Vol. 13, No. 3, 26.03.2019, p. 3545-3554.

Research output: Contribution to journalArticle

Xu, Y, Jiang, S, Simmons, CR, Narayanan, RP, Zhang, F, Aziz, AM, Yan, H & Stephanopoulos, N 2019, 'Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks' ACS Nano, vol. 13, no. 3, pp. 3545-3554. https://doi.org/10.1021/acsnano.8b09798
Xu Y, Jiang S, Simmons CR, Narayanan RP, Zhang F, Aziz AM et al. Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks. ACS Nano. 2019 Mar 26;13(3):3545-3554. https://doi.org/10.1021/acsnano.8b09798
Xu, Yang ; Jiang, Shuoxing ; Simmons, Chad R. ; Narayanan, Raghu Pradeep ; Zhang, Fei ; Aziz, Ann Marie ; Yan, Hao ; Stephanopoulos, Nicholas. / Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks. In: ACS Nano. 2019 ; Vol. 13, No. 3. pp. 3545-3554.
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