Multi-stage controlled structure of DNA-protein complex.

In the natural evolution, biomoleculars have developed a unique set of "bottom-up" self-assembling methods for the controlled assembly of various composite structures, which provides an excellent example for the processing and preparation of multi-functional bionanomaterials.
, the controlled construction of nucleic acid-protein nano-composite system will not only realize the effective combination of two basic assembly modes in biology to provide more complex biostructure templates, but also contribute to the in-depth understanding of the interaction of biomoleculars in the body, which is of far-reaching significance to the manufacture and biomedical application of bionic devices.
in recent years, DNA nanotechnology has achieved many remarkable research results.
researchers, with the help of a computer, constructed a series of delicate DNA multidimensional structures based on the principle of complementary base pairing, using their outstretched DNA to capture the dna fragments of the interbreeding protein surface, which can guide the protein object to be arranged in an orderly manner at a predetermined location, thus being widely used in the programmable structure of the DNA-protein composite nanostructure.
however, the conventional method of using protein surface amino acid residues for DNA co-pricing, there are some difficult to avoid, including the damage to functional protein activity of the modified group, the uncontrollability of modification points and orientation, and the inability of the operating system to the self-assembly process in the body, which limit further development.
, some scientists use non-covalent crosslinking, such as streptomycin-biotin interactions, specific ligands and DNA binding proteins, to assemble DNA stents-protein complex nanostructures.
But these studies are often limited to binding arrangements on DNA stents by specific protein individuals and do not involve subsequent assembly regulation.
to build a more advanced and orderly DNA-protein complex structure and realize protein molecular hydrosemitic and in situ assembly regulation is an important challenge in the development of nucleic acids and protein-based hybrid bionanomaterials.
in response to this challenge, Wang Qiangbin, a researcher at the Suzhou Institute of Nanotechnology and NanoBionics of the Chinese Academy of Sciences, based on previous work (ACS Nano, 2018, 12,1673-1679; Adv.Mater., 2017, 29, 1606533; J.Am.Chem.Soc., 2016, 138, 1764-1767; Small, 2016, 12, 4955-4959; J.Am.Chem.Soc., 2015, 137,457-462; J.Am.Chem.Soc., 2013, 135,11441-11444.), the first time using viral protein and genomic RNA intrinsic mechanism to design an in-situ controlled assembly system on the DNA stent, demonstrated the multi-stage controlled structure of the DNA-protein complex.
virus is a typical kind of self-group, its assembly process has a high specificity and efficiency, can be used in a short time with weak bond synergy assembly to produce a large number of virus particles.
using tobacco mosaic virus (Tobacco mosaic virus, TMV) as a model system, the researchers explored the interaction of TMV genomic RNA and shell proteins under different conditions and their regulation of the assembly of viral particles.
TMV genome-specific assembly starting sequence can effectively guide the specific binding of nucleic acids and viral shell proteins and trigger in vitro reconstruction assembly, and the assembly length of the viral protein tube is determined by RNA length, thus providing the possibility for precise regulation of the protein domain.
researchers constructed a 1D to 3D DNA origami template as a stent combined with different lengths of TMV RNA recombination sequence to guide the subsequent in-situ assembly process.
through the design of stent surface binding site and sequence, not only realizes the TMV virus protein tube in a specific location of THE DNA stent according to a certain assembly procedure for directional assembly growth, but also completes the effective regulation of the protein tube in situ assembly length.
these results provide a new strategy for building complex DNA-protein assembly systems.
this strategy is universal and demonstrates the potential for virus assembly and infection mechanism research with DNA origami as a functional carrier combined with other probes, providing a new perspective for the application of DNA nanotechnology in the biomedical field.
in the journal American Chemical Society (J.Am.Chem.Soc., 2018, DOI: 10.1021/jacs.8b03914).
this work is supported by the National Natural Science Foundation of China (21425103, 21673280, 21703282) and the National Key Research and Development Program (2016 YFA0101503, 2017YFA0205503).
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