Because of the simplicity and regularity of the alpha-helical coiled coil
relative to other structural motifs, it can be conveniently used to clarify the
molecular interactions responsible for protein folding and stability. Here we
describe the de novo design and characterization of a two heptad-repeat peptide
stabilized by a complex network of inter- and intrahelical salt bridges.
Circular dichroism spectroscopy and analytical ultracentrifugation show that
this peptide is highly alpha-helical and 100% dimeric tinder physiological
buffer conditions. Interestingly, the peptide was shown to switch its
oligomerization state from a dimer to a trimer upon increasing ionic strength.
The correctness of the rational design principles used here is supported by
details of the atomic structure of the peptide deduced from X-ray
crystallography. The structure of the peptide shows that it is not a molten
globule but assumes a unique, native-like conformation. This de novo peptide
thus represents an attractive model system for the design of a molecular
recognition system.
