Segregated Protein–Cucurbit[7]uril Crystalline Architectures via Modulatory Peptide Tectons

One approach to protein assembly involves water‐soluble supramolecular receptors that act like glues. Bionanoarchitectures directed by these scaffolds are often system‐specific, with few studies investigating their customization. Herein, the modulation of cucurbituril‐mediated protein assemblies through the inclusion of peptide tectons is described. Three peptides of varying length and structural order were N‐terminally appended to RSL, a β‐propeller building block. Each fusion protein was incorporated into crystalline architectures mediated by cucurbit[7]uril (Q7). A trimeric coiled‐coil served as a spacer within a Q7‐directed sheet assembly of RSL, giving rise to a layered material of varying porosity. Within the spacer layers, the coiled‐coils were dynamic. This result prompted consideration of intrinsically disordered peptides (IDPs) as modulatory tectons. Similar to the coiled‐coil, a mussel adhesion peptide (Mefp) also acted as a spacer between protein–Q7 sheets. In contrast, the fusion of a nucleoporin peptide (Nup) to RSL did not recapitulate the sheet assembly. Instead, a Q7‐directed cage was adopted, within which disordered Nup peptides were partially “captured” by Q7 receptors. IDP capture occurred by macrocycle recognition of an intrapeptide Phe‐Gly motif in which the benzyl group was encapsulated by Q7. The modularity of these protein–cucurbituril architectures adds a new dimension to macrocycle‐mediated protein assembly. Segregated protein crystals, with alternating layers of high and low porosity, could provide a basis for new types of materials. Bio‐supramolecular tectonics. The bionanoarchitectures of a β‐propeller protein and cucurbit[7]uril (Q7) were customized by incorporating peptide tectons. Segregated crystalline assemblies with alternating rigid and flexible layers were obtained. The flexible spacer layer could be achieved with either structured (coiled‐coil) or disordered (mussel foot peptide) tectons fused to the β‐propeller protein. A protein–Q7 cage‐like architecture partially captured a disordered nucleoporin peptide.