title: Reversible assembly of helical filaments by de novo designed minimalist peptides.
abstract: We have designed a series of 15 short, helical de novo peptides consisting of lysine, isoleucine, and alanine. We have termed this the KIA series. These peptides differ only in their hydrophobic interface, and thus their self-association is largely a consequence of hydrophobic interactions. One of these peptides, KIA13, forms insoluble helical fibers at specific NaCl concentrations. We have used CD spectroscopy, turbidity assays, and in situ tapping mode atomic force microscopy to characterize the reversible assembly pathway for this peptide. It is unfolded at low NaCl concentration, and forms helical, soluble fibers resembling a coiled-coil conformation at intermediate NaCl concentrations, and rope-like insoluble fibers at high NaCl concentrations. Reducing the NaCl concentration completely reverses this process. Another peptide from the KIA series specifically inhibits the formation of the insoluble KIA13 fibers, and reverses the process to some extent. This work sheds light onto protein fibrillogenesis and offers intriguing possibilities for the use of these types of peptides in drug delivery and biomaterials applications.
authors.affiliation: Division of Molecular and Structural Biology, Ontario Cancer Institute, and Departments of Medical Biophysics and Biochemistry, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada, M5G 2M9.
authors.forename: David W H
authors.initials: DW
authors.lastname: Frost
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yip
authors.forename: Avijit
authors.initials: A
authors.lastname: Chakrabartty
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D007532:Isoleucine; D008239:Lysine; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009391:Nephelometry and Turbidimetry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions
chemical_list: D010455:Peptides; D012996:Solutions; D007532:Isoleucine; D008239:Lysine; D000409:Alanine