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TitleDesign of coiled-coil protein-origami cages that self-assemble in vitro and in vivo.
Journal, issue, pagesNat Biotechnol, Vol. 35, Issue 11, Page 1094-1101, Year 2017
Publish dateOct 16, 2017
AuthorsAjasja 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 AbstractPolypeptides 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 linksNat Biotechnol / PubMed:29035374
MethodsEM (single particle)
Resolution19.0 - 28.0 Å
Structure data

EMDB-3781:
TET12SN density map (Design of in vivo self-assembling coiled-coil protein origami)
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-3788:
PYR16SN density map (Design of in vivo self-assembling coiled-coil protein origami)
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-3789:
TRIP18SN density map (Design of in vivo self-assembling coiled-coil protein origami)
Method: EM (single particle) / Resolution: 26.0 Å

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