Supramolecular Assembly and Small-Molecule Binding by Protein-Engineered Coiled-Coil Fibers

Dustin Britton, Julia Monkovic, Sihan Jia, Chengliang Liu, Farbod Mahmoudinobar, Michael Meleties, P. Douglas Renfrew, Richard Bonneau, Jin Kim Montclare

Research output: Contribution to journalArticlepeer-review


The ability to engineer a solvent-exposed surface of self-assembling coiled coils allows one to achieve a higher-order hierarchical assembly such as nano- or microfibers. Currently, these materials are being developed for a range of biomedical applications, including drug delivery systems; however, ways to mechanistically optimize the coiled-coil structure for drug binding are yet to be explored. Our laboratory has previously leveraged the functional properties of the naturally occurring cartilage oligomeric matrix protein coiled coil (C), not only for its favorable motif but also for the presence of a hydrophobic pore to allow for small-molecule binding. This includes the development of Q, a rationally designed pentameric coiled coil derived from C. Here, we present a small library of protein microfibers derived from the parent sequences of C and Q bearing various electrostatic potentials with the aim to investigate the influence of higher-order assembly and encapsulation of candidate small molecule, curcumin. The supramolecular fiber size appears to be well-controlled by sequence-imbued electrostatic surface potential, and protein stability upon curcumin binding is well correlated to relative structure loss, which can be predicted by in silico docking.

Original languageEnglish (US)
Pages (from-to)4851-4859
Number of pages9
Issue number11
StatePublished - Nov 14 2022

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


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