Variable stability heterodimeric coiled-coils from manipulation of electrostatic interface residue chain length.
The design of variable-stability coiled-coil heterodimers is described. The electrostatic interface between helices, formed by contact between side chains in heptad e/g positions, is manipulated to produce complexes ranging in stability from ones that are essentially unstructured to those that cannot be thermally denatured. The tuning is accomplished by incremental extension or contraction of parent glutamic acid and lysine side chains by single methylene units, producing peptides that bear either carboxylic acids or amines separated from the peptide backbone by one to four CH2 groups. Detailed examination of all homodimers and electrostatically compatible heterodimers generates interesting combinations, particularly those in which longer-chain acids are incorporated into peptides paired with lysine-bearing ones. The discovery of very stable dimers allows exchange experiments in which one strand of an original heterodimer is specifically replaced by an added one, even in cases where the original complex features the native-like glutamic acid/lysine pairing. The reported results add significantly to the available design templates for coiled-coil construction and enable the future implementation of various triggered-recognition strategies.
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Shannon J
SJ
Ryan
Alan J
AJ
Kennan
D000595:Amino Acid Sequence; D019281:Dimerization; D018698:Glutamic Acid / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D055672:Static Electricity; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000737:chemistry
D009942:Organometallic Compounds; D010455:Peptides; D015091:beta-Alanine; C088321:nickel nitrilotriacetic acid; D018698:Glutamic Acid; C011757:2,3-diaminopropionic acid; D008239:Lysine; D009571:Nitrilotriacetic Acid