Self-Assembling Cages from Coiled-Coil Peptide Modules

By Jordan M. Fletcher, R. Harniman, Frederick R. H. Barnes, A. Boyle, A. Collins, J. Mantell, T. Sharp, M. Antognozzi, P. Booth, Noah Linden and 4 more. 2013

448 citations recorded by the source corpus.

From Coils to Cages Self-assembly strategies that mimic protein assembly, such as the formation of viral coats, often begin with simpler peptide assemblies. Fletcher et al. (p. 595, published online 11 April; see the Perspective by Ardejani and Orner) designed two coiled-coil peptide motifs, a heterodimer, and a homotrimer. Both peptides contained cysteine residues and could link through disulfide bonds, so that the trimer could form the vertices of a hexagonal network and the dimer its edges. However, these components are flexible and, rather than form extended sheets, they closed to form particles ∼100 nanometers in diameter. Hexagonal networks form from heterodimeric and homotrimeric coiled coils and create ~100-nanometer-diameter cages. [Also see Perspective by Ardejani and Orner] An ability to mimic the boundaries of biological compartments would improve our understanding of self-assembly and provide routes to new materials for the delivery of drugs and biologicals and the development of protocells. We show that short designed peptides can be combined to form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric and homotrimeric coiled-coil bundles. These are joined back to back to render two complementary hubs, which when mixed form hexagonal networks that close to form cages. This design strategy offers control over chemistry, self-assembly, reversibility, and size of such particles.

Subfields: Biomaterials, Molecular Biology

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Citations in the corpus

The coming of age of de novo protein design (2016, background): “4), including a peptide that binds to carbon nano-tubes 53 , parallel self-assembling helical channels 31 , an ion transporter 34 , cages 54 and an α-helical barrel with installed hydrolytic activity 55 .”
Design of a hyperstable 60-subunit protein icosahedron (2016, unknown): “Protein assemblies have been engineered using metals 9,10 , disulfide bonds 11–14 , genetic fusions 12,15–17 , and ideal helix-helix interactions 11,13,16 , but these approaches have generally yielded polydisperse or unanticipated products.”
De novo protein design, a retrospective (2020, background): “…of cages by combining multiple symmetry elements The predictable nature and robustness of coiled-coil assemblies was expanded to form large cages (Fletcher et al., 2013) as well as distinct supramolecular polyhedral nanostructures that can assemble both in vitro and in vivo (Gradišar et al.,…”