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Computational Design Of Protein-DNA Nanowires

Mou, Yun (2014) Computational Design Of Protein-DNA Nanowires. Protein Science, 23 (S1). pp. 152-153. ISSN 0961-8368. doi:10.1002/pro.2504.

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Computation protein design (CPD) has been successfully used to create various functional proteins, including enzymes, protein binders, ligand binders, and protein self-assemblies. The ability to rationally design molecular self-assembly using biological macromolecules is of particular interest because of the potential for applications in biotechnology and medicine. Sophisticated single-component nanostructures composed exclusively of nucleic acids or proteins have been demonstrated, but despite these successes, the development of hybrid self-assemblies of nucleic acids and proteins via non-covalent interactions remains elusive. Here, we used CPD to create a protein-DNA complex that can self-assemble into nanowires. To achieve this, a homodimerization interface was engineered onto the Drosophila Engrailed homeodomain (ENH) transcription factor so that the complex could bind two DNA molecules. The homodimerization interface was designed de novo, whereas ENH’s native DNA-binding interface was exploited to bind a specific double-stranded DNA (dsDNA) motif. When dsDNA fragments containing two protein-binding motifs on opposite faces of the DNA were combined with the engineered ENH homodimer, the two components self-assembled to form protein-DNA nanowires. Atomic force microscopy showed that the diameter of the nanowire is approximately 10 nm, which is consistent with the length of the dsDNA fragment. The length of the nanowire is up to 300 nm. A protein-DNA co-crystal structure confirmed that the nanowire is formed via the designed interactions.

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Additional Information:© 2014 The Protein Society. Article first published online: 10 Jul 2014.
Issue or Number:S1
Record Number:CaltechAUTHORS:20140822-090440205
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Official Citation:Special Issue: The 28th Annual Symposium of The Protein Society, San Diego, CA, USA, July 27–30, 2014 Volume 23, Issue S1, pages 1–284, July 2014
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48799
Deposited By: Ruth Sustaita
Deposited On:22 Aug 2014 20:14
Last Modified:10 Nov 2021 18:36

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