DNA Nanodevices as Mechanical Probes of Protein Structure and Function
Source abstract
Abstract
DNA nanotechnology has reported a wide range of structurally tunable scaffolds with precise control over their size, shape and mechanical properties. One promising application of these nanodevices is as probes for protein function or determination of protein structure. In this perspective we cover several recent examples in this field, including determining the effect of ligand spacing and multivalency on cell activation, applying forces at the nanoscale, and helping to solve protein structure by cryo-EM. We also highlight some future directions in the chemistry necessary for integrating proteins with DNA nanoscaffolds, as well as opportunities for computational modeling of hybrid protein-DNA nanomaterials.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA and protein synthesis mechanisms · Bacteriophages and microbial interactions
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA
Biodesign Center for Molecular Design and Biomimetics, Arizona State University, Tempe, AZ 85281, USA
Funding
National Science Foundation
References (82)
Show source-provided references
1. Folding DNA to create nanoscale shapes and patterns
2. Self-assembly of DNA into nanoscale three-dimensional shapes
3. Functionalization of DNA nanostructures with proteins10.1039/c1cs15212b ↗
4. Chemistries for DNA Nanotechnology10.1021/acs.chemrev.8b00570 ↗
5. Functionalized DNA Nanostructures10.1021/cr200104q ↗
6. Hybrid Nanostructures from the Self-Assembly of Proteins and DNA10.1016/j.chempr.2020.01.012 ↗
7. Nucleic acid junctions and lattices10.1016/0022-5193(82)90002-9 ↗
8. Challenges and opportunities for structural DNA nanotechnology10.1038/nnano.2011.187 ↗
9. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal
10. Tuning the Cavity Size and Chirality of Self-Assembling 3D DNA Crystals10.1021/jacs.7b06485 ↗
11. Construction and Structure Determination of a Three-Dimensional DNA Crystal10.1021/jacs.6b06508 ↗
12. A Self-Assembled Rhombohedral DNA Crystal Scaffold with Tunable Cavity Sizes and High-Resolution Structural Detail10.1002/anie.202005505 ↗
13. Three-Dimensional DNA Crystals as Molecular Sieves10.1021/ja061322r ↗
14. DNA Crystals as Vehicles for Biocatalysis10.1021/ja502356m ↗
15. Design of a molecular support for cryo-EM structure determination10.1073/pnas.1612720113 ↗
16. Aksel, T., Yu, Z., Cheng, Y., and Douglas, S.M. (2020). Molecular goniometers for single-particle cryo-electron microscopy of DNA-binding proteins. Nat. Biotechnol., 1–9.10.1101/2020.02.27.968883 ↗
17. Engineering a 2D Protein-DNA Crystal10.1002/anie.200463027 ↗
18. DNA-Templated Protein Arrays for Single-Molecule Imaging10.1021/nl1037769 ↗
19. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra
20. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron
21. Cryo-EM structure of a 3D DNA-origami object10.1073/pnas.1215713109 ↗
22. Folding DNA into a Lipid-Conjugated Nanobarrel for Controlled Reconstitution of Membrane Proteins10.1002/ange.201710147 ↗
23. Revealing the structures of megadalton-scale DNA complexes with nucleotide resolution10.1038/s41467-020-20020-7 ↗
24. Sequence-programmable covalent bonding of designed DNA assemblies10.1126/sciadv.aau1157 ↗
25. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures10.1093/nar/gkr1173 ↗
26. Spatial control of membrane receptor function using ligand nanocalipers10.1038/nmeth.3025 ↗
27. Role of nanoscale antigen organization on B-cell activation probed using DNA origami10.1038/s41565-020-0719-0 ↗
28. A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement10.1021/acsnano.7b08044 ↗
29. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex10.1038/s41467-018-03313-w ↗
30. Organizing protein–DNA hybrids as nanostructures with programmed functionalities10.1016/j.tibtech.2010.09.005 ↗
31. Nucleic-Acid-Templated Enzyme Cascades10.1002/cbic.201600703 ↗
32. Linko, V., Nummelin, S., Aarnos, L., Tapio, K., Toppari, J.J., and Kostiainen, M.A. (2016). DNA-Based Enzyme Reactors and Systems. Nanomaterials, 6.10.3390/nano6080139 ↗
33. Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies10.1038/s41565-018-0336-3 ↗
34. DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels10.1002/anie.201709982 ↗
35. Proximity-induced caspase-9 activation on a DNA origami-based synthetic apoptosome10.1038/s41929-019-0403-7 ↗
36. DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens10.1073/pnas.2016857118 ↗
37. Tug-of-War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold10.1126/science.1226734 ↗
38. Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments10.1038/nnano.2015.132 ↗
39. A Programmable DNA Origami Platform to Organize SNAREs for Membrane Fusion10.1021/jacs.5b13107 ↗
40. Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling10.1126/science.1231041 ↗
41. DNA-based digital tension probes reveal integrin forces during early cell adhesion10.1038/ncomms6167 ↗
42. Placing molecules with Bohr radius resolution using DNA origami10.1038/nnano.2015.240 ↗
43. Molecular force spectroscopy with a DNA origami–based nanoscopic force clamp10.1126/science.aah5974 ↗
44. Rapid Photoactuation of a DNA Nanostructure using an Internal Photocaged Trigger Strand10.1002/anie.201804264 ↗
45. Programmable motion of DNA origami mechanisms10.1073/pnas.1408869112 ↗
46. Paper Origami-Inspired Design and Actuation of DNA Nanomachines with Complex Motions10.1002/smll.201802580 ↗
47. DNA Nunchucks: Nanoinstrumentation for Single-Molecule Measurement of Stiffness and Bending10.1021/acs.nanolett.9b04980 ↗
48. Self-Assembly of Precisely Defined DNA Nanotube Superstructures Using DNA Origami Seeds10.1039/C6NR06983E ↗
49. Probing Nucleosome Stability with a DNA Origami Nanocaliper10.1021/acsnano.6b03218 ↗
50. Exploring Nucleosome Unwrapping Using DNA Origami10.1021/acs.nanolett.6b04169 ↗
51. Uncovering the forces between nucleosomes using DNA origami10.1126/sciadv.1600974 ↗
52. A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads10.1038/ncomms13715 ↗
53. Folding DNA into Twisted and Curved Nanoscale Shapes10.1126/science.1174251 ↗
54. Inequivalence of fixed-force and fixed-extension statistical ensembles for a flexible polymer tethered to a planar substrate10.1039/C8SM01321G ↗
55. Measuring Internal Forces in Single-Stranded DNA: Application to a DNA Force Clamp10.1021/acs.jctc.0c00286 ↗
56. SNAP-Tag Technology: A General Introduction10.2174/13816128113199990514 ↗
57. Tunable Nanoscale Cages from Self-Assembling DNA and Protein Building Blocks10.1021/acsnano.8b09798 ↗
58. Hierarchical Assembly of Nucleic Acid/Coiled-Coil Peptide Nanostructures10.1021/jacs.9b11158 ↗
59. A covalent and cleavable antibody-DNA conjugation strategy for sensitive protein detection via immuno-PCR10.1038/srep22675 ↗
60. Template-directed covalent conjugation of DNA to native antibodies, transferrin and other metal-binding proteins10.1038/nchem.2003 ↗
61. Docking of Antibodies into the Cavities of DNA Origami Structures10.1002/anie.201706765 ↗
62. Tailored protein encapsulation into a DNA host using geometrically organized supramolecular interactions10.1038/ncomms14472 ↗
63. Macromolecular Modeling with Rosetta10.1146/annurev.biochem.77.062906.171838 ↗
64. Rapid prototyping of 3D DNA-origami shapes with caDNAno10.1093/nar/gkp436 ↗
65. Jun, H., Wang, X., Bricker, W.P., Jackson, S., and Bathe, M. (2020). Rapid Prototyping of Wireframe Scaffolded DNA Origami using ATHENA. bioRxiv.10.1101/2020.02.09.940320 ↗
66. Adenita: Interactive 3D modelling and visualization of DNA nanostructures10.1093/nar/gkaa593 ↗
67. Design, optimization and analysis of large DNA and RNA nanostructures through interactive visualization, editing and molecular simulation10.1093/nar/gkaa417 ↗
68. Coarse-graining DNA for simulations of DNA nanotechnology10.1039/c3cp53545b ↗
69. GROMACS: Fast, flexible, and free10.1002/jcc.20291 ↗
70. Scalable molecular dynamics with NAMD10.1002/jcc.20289 ↗
71. ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB10.1021/acs.jctc.5b00255 ↗
72. Parmbsc1: A refined force field for DNA simulations10.1038/nmeth.3658 ↗
73. Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions10.1021/acs.jctc.8b00955 ↗
74. De novoreconstruction of DNA origami structures through atomistic molecular dynamics simulation10.1093/nar/gkw155 ↗
75. Molecular dynamics simulations of DNA-DNA and DNA-protein interactions10.1016/j.sbi.2020.06.007 ↗
76. MARTINI-Based Protein-DNA Coarse-Grained HADDOCKing10.3389/fmolb.2019.00102 ↗
77. Lu, W., Bueno, C., Schafer, N.P., Moller, J., Jin, S., Chen, X., Chen, M., Gu, X., Davtyan, A., and de Pablo, J.J. (2021). OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations. PLoS Comput. Biol., 17.10.1371/journal.pcbi.1008308 ↗
78. Procyk, J., Poppleton, E., and Šulc, P. (2020). Coarse-grained nucleic acid–protein model for hybrid nanotechnology. Soft Matter.10.1039/D0SM01639J ↗
79. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA10.1063/1.4921957 ↗
80. Sequence-dependent thermodynamics of a coarse-grained DNA model10.1063/1.4754132 ↗
81. Structural, mechanical, and thermodynamic properties of a coarse-grained DNA model10.1063/1.3552946 ↗
82. Multiscale Gaussian network model (mGNM) and multiscale anisotropic network model (mANM)10.1063/1.4936132 ↗