Identification of stable helical bundles from a combinatorial library of amphipathic peptides.
A set of combinatorial amphipathic helical peptides referred to as the KIA series has been screened to identify native-like helical bundles. The series contains the following consensus sequence: AKAxAAxxKAxAAxxKAGGY, where "x" positions are occupied by either Ala or Ile. The peptide sequences in the series comprise all possible combinations of four Ile residues occupying the six x positions. In each case, Ala occupied the two x positions not occupied by Ile. There are a total of 15 peptides in the KIA series; all of the peptides differ in the number of ridges and grooves formed by the Ile side chains, and two of the KIA peptides possess a canonical knobs-into-holes heptad repeat. The structure and stability of these 15 peptides and their pairwise mixtures were evaluated. One peptide in the series formed a stable four-helix bundle that folded with cooperativity similar to native proteins. Ten peptides assembled into molten globular helical assemblies, two peptides were unstructured, and two peptides assembled into helical filaments that were several micrometers long. One of the helical filament forming peptides could be diverted from forming filaments by the addition of another KIA peptide, and resulted in the formation of a heteromeric six-helix bundle. This study demonstrates that combinatorial peptides composed of only three types of amino acids can form a diverse array of structures, some of which are native-like.
Boon
Chandra L
CL
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.
Frost
David
D
Chakrabartty
Avijit
A
D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary
D019151:Peptide Library; D010455:Peptides