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Title | Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo. |
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Journal, issue, pages | Nat Biotechnol, Vol. 35, Issue 11, Page 1094-1101, Year 2017 |
Publish date | Oct 16, 2017 |
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 / |
PubMed 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 ...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. |
External links | Nat Biotechnol / PubMed:29035374 |
Methods | SAS (X-ray synchrotron) / EM (single particle) |
Resolution | 19.0 - 28.0 Å |
Structure data | SASDBS9: SASDCR7: SASDCS7: SASDCT7: SASDCU7: SASDCV7: SASDCW7: SASDCX7: SASDCY7: SASDCZ7: EMDB-3781: EMDB-3788: EMDB-3789: |
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