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 smallmolecule 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.
A wide class of neurodegenerative disorders is due to the failure of a peptide or protein to keep its native functional conformational state and undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-b sheet amyloid aggregates. Tremendous efforts have been devoted in the last twenty years with the aim to understand the molecular basis of Alzheimer's disease and to develop small molecules that could interfere with the aggregation pathway of Ab peptides. Several disease-modifying small mole-
Previously reported, Q, is a thermoresponsive coiled-coil protein capable of higher-order supramolecular assembly into fibers and hydrogels with upper critical solution temperature (UCST) behavior. Here, we introduce a new coiled-coil...
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