Functional Coiled-Coil-like Assembly by Knob-into-Hole Packing of Single Heptad Repeat

Coiled-coil peptides represent the
principal building blocks for
structure-based design of bionanomaterials. The sequence–structure
relationship and precise nanoscale ordering of the coiled-coil helices
originate from the knob-into-hole (KIH) packing of side chains. The
helical interface stabilized by the KIH interaction is known to have
chain lengths ranging from 30 to 1000 residues. Yet the shortest peptide
required for oligomerization through KIH assembly is still unknown.
Here, we report that through atomic resolution a minimal seven-residue
amphipathic helix forms a different type of KIH motif, termed “supramolecular
KIH packing”, which confers an exceptional stability to the
helical dimers. Significantly, at a low pH, the peptide self-assembles
into nanofibers with coiled-coil architecture resembling the natural
fibrous proteins. Furthermore, hierarchical ordering of the nanofibers
affords lyotropic liquid crystals composed of a shortest natural helical
sequence. Thus, this study expands the sequence space for a coiled-coil
folding manifold and provides another paradigm for designer nanomaterials
from minimal helical sequences.