4QTR

Computational design of co-assembling protein-DNA nanowires

4QTR の概要

• エントリーDOI: 10.2210/pdb4qtr/pdb
• 分子名称: 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)
• 機能のキーワード: helix-turn-helix, dna-binding protein, double-stranded dna, de novo design-dna complex, de novo design/dna
• 由来する生物種: Drosophila melanogaster
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 54320.50

構造登録者

Mou, Y.,Mayo, S.L. (登録日: 2014-07-08, 公開日: 2015-07-29, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.2 Å)