Specific control of peptide assembly with combined hydrophilic and hydrophobic interfaces.
Designed coiled-coil heterotrimers are described whose assembly is governed by both hydrophobic and hydrophilic forces. Sterically matched hydrophobic core side-chain packing of alanine and cyclohexylalanine has been shown to promote formation of a 1:1:1 heterotrimer. Manipulation of hydrophilic glutamic acid (Glu)/lysine (Lys) pairs at each of three helical contact interfaces provides a secondary recognition mechanism. Peptides with matched cores and hydrophilic contacts form stable heterotrimers (DeltaG(unf) at 25 degrees C = 17.93 kcal/mol; MW(app) = 11362 vs 11563 calcd for trimer), as do those with a single Lys/Lys (but not Glu/Glu) interface. The additional specificity engendered by simultaneous operation of two interfaces was used to design a system in which six different peptides are mixed to form three specific and independent heterotrimers in the same solution.
Schnarr
Nathan A
NA
Department of Chemistry, Colorado State University, Fort Collins 80523, USA.
Kennan
Alan J
AJ
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D010455:Peptides; C028544:cyclohexylalanine; D010649:Phenylalanine; D000409:Alanine