Design of a minimal protein oligomerization domain by a structural approach

Because of the simplicity and regularity of the Lu-helical coiled coil rela tive 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 br idges. Circular dichroism spectroscopy and analytical ultracentrifugation s how that this peptide is highly alpha -helical and 100% dimeric under physi ological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic st rength. The correctness of the rational design principles used here is supp orted 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 dr novo pepti de thus represents an attractive model system for the design of a molecular recognition system.