Computational design of co-assembling protein-DNA nanowires.
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.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Yun
Y
Mou
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Jiun-Yann
JY
Yu
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Timothy M
TM
Wannier
Division of Engineering and Applied Science, California Institute of Technology, Pasadena, California 91125, USA.
Chin-Lin
CL
Guo
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.|Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Stephen L
SL
Mayo
D001665:Binding Sites; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D029721:Drosophila Proteins; D015195:Drug Design; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D036103:Nanotechnology; D053770:Nanowires / Q000737:chemistry*; D055503:Protein Multimerization; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; D014157:Transcription Factors; D004247:DNA