Title |
Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo
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Published in |
Nature Biotechnology, October 2017
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DOI | 10.1038/nbt.3994 |
Pubmed ID | |
Authors |
Ajasja Ljubetič, Fabio Lapenta, Helena Gradišar, Igor Drobnak, Jana Aupič, Žiga Strmšek, Duško Lainšček, Iva Hafner-Bratkovič, Andreja Majerle, Nuša Krivec, Mojca Benčina, Tomaž Pisanski, Tanja Ćirković Veličković, Adam Round, José María Carazo, Roberto Melero, Roman Jerala |
Abstract |
Polypeptides and polynucleotides are natural programmable biopolymers that can self-assemble into complex tertiary structures. We describe a system analogous to designed DNA nanostructures in which protein coiled-coil (CC) dimers serve as building blocks for modular de novo design of polyhedral protein cages that efficiently self-assemble in vitro and in vivo. We produced and characterized >20 single-chain protein cages in three shapes-tetrahedron, four-sided pyramid, and triangular prism-with the largest containing >700 amino-acid residues and measuring 11 nm in diameter. Their stability and folding kinetics were similar to those of natural proteins. Solution small-angle X-ray scattering (SAXS), electron microscopy (EM), and biophysical analysis confirmed agreement of the expressed structures with the designs. We also demonstrated self-assembly of a tetrahedral structure in bacteria, mammalian cells, and mice without evidence of inflammation. A semi-automated computational design platform and a toolbox of CC building modules are provided to enable the design of protein cages in any polyhedral shape. |
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Geographical breakdown
Country | Count | As % |
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United States | 16 | 16% |
Slovenia | 11 | 11% |
United Kingdom | 8 | 8% |
Japan | 4 | 4% |
Netherlands | 3 | 3% |
Spain | 3 | 3% |
India | 2 | 2% |
Korea, Republic of | 2 | 2% |
Germany | 2 | 2% |
Other | 12 | 12% |
Unknown | 38 | 38% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 66 | 65% |
Scientists | 34 | 34% |
Science communicators (journalists, bloggers, editors) | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 353 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 88 | 25% |
Researcher | 51 | 14% |
Student > Bachelor | 39 | 11% |
Student > Master | 33 | 9% |
Student > Doctoral Student | 16 | 5% |
Other | 48 | 14% |
Unknown | 78 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 105 | 30% |
Chemistry | 58 | 16% |
Agricultural and Biological Sciences | 52 | 15% |
Engineering | 13 | 4% |
Materials Science | 10 | 3% |
Other | 34 | 10% |
Unknown | 81 | 23% |