Peptide Assemblies Mimicking Chaperones for Protein Trafficking

Although peptide assemblies have been explored extensively, the self-assembly of negatively charged peptides (NCPs) received little attention. Stimulated by the fact that acidic stretch is a common feature in the intrinsically disordered regions of histone chaperones, we explored the use of the assemblies of NCPs for trafficking histone proteins. Our results show that the peptides that contain glutamic acid (E)-repeat, at neutral or basic pH, self-assemble to form micelles in solution. Circular dichroism indicates that increasing pH favored the peptides to populate more in disordered and α helix conformations. Being innocuous to cells, the assemblies of these NCPs traffic histone 2B (H2B) to mitochondria. Structure-activity study indicates that self-assembly, proper stereochemistry, and acidic repeats are necessary for trafficking H2B. This work, as the first example of peptide assemblies for protein trafficking, illustrates a supramolecular approach for controlling cellular processes and provides insights for mimicking chaperones and controlling protein-protein interactions.