TY - JOUR
T1 - Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks
AU - Xu, Yang
AU - Jiang, Shuoxing
AU - Simmons, Chad R.
AU - Narayanan, Raghu Pradeep
AU - Zhang, Fei
AU - Aziz, Ann Marie
AU - Yan, Hao
AU - Stephanopoulos, Nicholas
N1 - Funding Information:
N.S. gratefully acknowledges startup funds from Arizona State University. This material is based upon work supported by the Air Force Office of Scientific Research under award number FA9550-17-1-0053. The authors thank Prof. Matthew B. Francis for providing the plasmids for noncanonical amino acid incorporation.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/3/26
Y1 - 2019/3/26
N2 - 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.
AB - 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.
KW - 3D nanocages
KW - DNA nanotechnology
KW - DNprotein bioconjugation
KW - DNprotein hybrids
KW - aldolase trimer
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U2 - 10.1021/acsnano.8b09798
DO - 10.1021/acsnano.8b09798
M3 - Article
C2 - 30835439
AN - SCOPUS:85063151355
SN - 1936-0851
VL - 13
SP - 3545
EP - 3554
JO - ACS nano
JF - ACS nano
IS - 3
ER -