Arginine tuning of coiled-coil peptides yields single-domain nanocrystals

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Abstract
Programming three-dimensional order in peptide-based materials requires lateral interactions that are precise enough to propagate over hundreds of nanometres, yet robust enough to operate in water. Here, we show that a rationally designed coiled-coil peptide meets both demands by assembling into a hierarchical suprahelix that promotes spontaneous crystallisation under physiological buffer conditions. Coiled-coil dimers wind around one another to generate the higher-order suprahelix. Subtle lysine-to-arginine substitutions tune lateral cohesion, revealing a non-monotonic dependence on arginine density: 46-residue peptides with three or six arginine residues form ellipsoidal nanocrystals, whereas arginine-free or arginine-rich variants form amorphous aggregates. Time-resolved spectroscopy and cryogenic electron microscopy show that crystallisation proceeds by a non-classical pathway, in which condensed protofibrils align before consolidating into an ordered lattice. Cryo-electron tomography supports the single-domain nature of the resulting nanocrystals, and three-dimensional electron diffraction shows that both crystalline variants adopt the same near hexagonal unit-cell metrics. These findings translate a principle from protein crystallography, that arginine favours crystal contacts relative to lysine, into a sequence-level design parameter for coiled-coil nanocrystallization, providing a route to programmable three-dimensional order in soft molecular materials.

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