Biomolecules on spokes
From DNA and proteins learned to weave tangles and threads
Bioengineers from the California Institute of Technology (Caltech) have learned how to create non-covalent complexes in the form of threads and tangles from DNA and special proteins. The type of complexes formed can be controlled by changing the DNA sequence. The work was published in Nature (Mou et al., Computational design of co-assembling protein–DNA nanowires).
Both strands and tangles consist of two components: short double-stranded DNA and proteins that bind them to each other. This binding, although quite strong, is still not covalent, that is, it does not imply the formation of new chemical bonds. Proteins are fixed to DNA by hydrogen bonds – exactly the same as it happens when DNA is bound by natural proteins, for example, transcription factors (these are proteins that control the work of genes, activating the synthesis of RNA on the DNA matrix).
The protein that the authors used to create the threads is, in fact, a modification of one of the natural proteins. We are talking about one of the transcription factors first discovered in drosophila and controlling embryonic development (engraved homeodomain, ENH).
During the modification, the authors conducted a computer simulation of the interaction of two molecules of this protein with the formation of a head-to-head dimer. Molecular docking made it possible to identify those amino acids that provide the strongest possible interaction of the "heads" of two molecules with each other, but at the same time do not interfere with the work of natural DNA-binding "tails".
After the computer "design" of the molecules was completed, the proteins were synthesized in a recombinant system, isolated and used to form complexes with DNA. The result was examined using fluorescence and atomic force microscopy, as well as X-ray analysis.
The synthetic protein was indeed able to form extended strands or tangles; what exactly happened in this case depended on the location of the protein landing sites on the DNA fragments used. Since the chemical synthesis of short DNA of arbitrary sequence is very cheap nowadays, it is not difficult to control the type of DNA protein polymers.
The principle of binding DNA and protein dimers in a chain.
An image from an article in Nature.
The authors consider the new system as another tool for creating biocompatible nanodevices – along with numerous versions of DNA origami technology.
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07.09.2015