4QTR

Computational design of co-assembling protein-DNA nanowires

Summary for 4QTR

• Entry DOI: 10.2210/pdb4qtr/pdb
• Descriptor: dualENH, DNA (5'-D(P*GP*TP*GP*TP*AP*AP*TP*TP*TP*AP*AP*TP*TP*TP*CP*C)-3'), DNA (5'-D(P*CP*GP*GP*AP*AP*AP*TP*TP*AP*AP*AP*TP*TP*AP*CP*A)-3') (3 entities in total)
• Functional Keywords: helix-turn-helix, dna-binding protein, double-stranded dna, de novo design-dna complex, de novo design/dna
• Biological source: Drosophila melanogaster
• Total number of polymer chains: 8
• Total formula weight: 54320.50

Authors

Mou, Y.,Mayo, S.L. (deposition date: 2014-07-08, release date: 2015-07-29, Last modification date: 2023-09-20)

Primary citation

Mou, Y.,Yu, J.Y.,Wannier, T.M.,Guo, C.L.,Mayo, S.L.
Computational design of co-assembling protein-DNA nanowires.
Nature, 525:230-233, 2015

PubMed Abstract: Biomolecular self-assemblies are of great interest to nanotechnologists because of their functional versatility and their biocompatibility. Over the past decade, sophisticated single-component nanostructures composed exclusively of nucleic acids, peptides and proteins have been reported, and these nanostructures have been used in a wide range of applications, from drug delivery to molecular computing. Despite these successes, the development of hybrid co-assemblies of nucleic acids and proteins has remained elusive. Here we use computational protein design to create a protein-DNA co-assembling nanomaterial whose assembly is driven via non-covalent interactions. To achieve this, a homodimerization interface is engineered onto the Drosophila Engrailed homeodomain (ENH), allowing the dimerized protein complex to bind to two double-stranded DNA (dsDNA) molecules. By varying the arrangement of protein-binding sites on the dsDNA, an irregular bulk nanoparticle or a nanowire with single-molecule width can be spontaneously formed by mixing the protein and dsDNA building blocks. We characterize the protein-DNA nanowire using fluorescence microscopy, atomic force microscopy and X-ray crystallography, confirming that the nanowire is formed via the proposed mechanism. This work lays the foundation for the development of new classes of protein-DNA hybrid materials. Further applications can be explored by incorporating DNA origami, DNA aptamers and/or peptide epitopes into the protein-DNA framework presented here.

PubMed: 26331548
DOI: 10.1038/nature14874

Experimental method

X-RAY DIFFRACTION (3.2 Å)