Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks

Yang Xu, Shuoxing Jiang, Chad R. Simmons, Raghu Pradeep Narayanan, Fei Zhang, Ann Marie Aziz, Hao Yan, Nicholas Stephanopoulos

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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
Issue number3
StatePublished - Mar 26 2019


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

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy


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