A Peptide Building Block for P-trefoil Protein Architecture

Protein folding is a poorly understood science, and therefore, protein engineering has yet to realize the functional potential inherent in proteins. Development of a useful "structural toolkit" for de novo protein design is a highly desirable, yet unrealized goal of the field.

A novel 42 amino acid polypeptide sequence has been designed that spontaneously assembles into a homo-trimer, forming a thermostable P-trefoil protein architecture. The polypeptide can also be ligated, to form three identical repeating sequences within a single polypeptide, which also spontaneously folds into a thermostable P-trefoil protein architecture. The peptide is thus useful for either de novo design, rational design, or directed evolution of novel proteins based upon the P-trefoil architecture. The Invention represents an initial successful example of the development of a useful peptide building block for a common protein architecture (the P-trefoil).

The peptide sequence was designed using a novel approach, and as a consequence there are an extremely limited number of useful related "building blocks" in protein design. The idea of a "structural toolkit" for protein design is largely conceptual; the current Invention is arguably one of the first successful examples.