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A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes

Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight str...

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Autores principales: Ohmann, Alexander, Li, Chen-Yu, Maffeo, Christopher, Al Nahas, Kareem, Baumann, Kevin N., Göpfrich, Kerstin, Yoo, Jejoong, Keyser, Ulrich F., Aksimentiev, Aleksei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013447/
https://www.ncbi.nlm.nih.gov/pubmed/29930243
http://dx.doi.org/10.1038/s41467-018-04821-5
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author Ohmann, Alexander
Li, Chen-Yu
Maffeo, Christopher
Al Nahas, Kareem
Baumann, Kevin N.
Göpfrich, Kerstin
Yoo, Jejoong
Keyser, Ulrich F.
Aksimentiev, Aleksei
author_facet Ohmann, Alexander
Li, Chen-Yu
Maffeo, Christopher
Al Nahas, Kareem
Baumann, Kevin N.
Göpfrich, Kerstin
Yoo, Jejoong
Keyser, Ulrich F.
Aksimentiev, Aleksei
author_sort Ohmann, Alexander
collection PubMed
description Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 10(7) molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.
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spelling pubmed-60134472018-06-25 A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes Ohmann, Alexander Li, Chen-Yu Maffeo, Christopher Al Nahas, Kareem Baumann, Kevin N. Göpfrich, Kerstin Yoo, Jejoong Keyser, Ulrich F. Aksimentiev, Aleksei Nat Commun Article Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 10(7) molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine. Nature Publishing Group UK 2018-06-21 /pmc/articles/PMC6013447/ /pubmed/29930243 http://dx.doi.org/10.1038/s41467-018-04821-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ohmann, Alexander
Li, Chen-Yu
Maffeo, Christopher
Al Nahas, Kareem
Baumann, Kevin N.
Göpfrich, Kerstin
Yoo, Jejoong
Keyser, Ulrich F.
Aksimentiev, Aleksei
A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title_full A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title_fullStr A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title_full_unstemmed A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title_short A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes
title_sort synthetic enzyme built from dna flips 10(7) lipids per second in biological membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013447/
https://www.ncbi.nlm.nih.gov/pubmed/29930243
http://dx.doi.org/10.1038/s41467-018-04821-5
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