Small is Functional

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Science  16 Mar 2001:
Vol. 291, Issue 5511, pp. 2049
DOI: 10.1126/science.291.5511.2049b

The synthesis of small, fully folded proteins has been advanced by an improved understanding of the factors driving secondary and tertiary structure formation and by combinatorial methods. The current challenge is making small proteins that function.

Chin and Schepartz have devised a method based on protein grafting to synthesize DNA-binding proteins just 35 residues in length. Protein grafting means that the functional residues are introduced into a scaffold with the dual goals of maintaining conformational stability and optimizing substrate binding. The scaffold was based on the solvent-exposed α-helix of avian pancreatic polypeptide, and the authors identified a miniature protein with high affinity for the target ATGAC sequence. The fold of the grafted protein resembles that of avian pancreatic polypeptide and suggests that this method also may be used to derive reduced versions of other proteins that utilize an α-helix for recognition. — JU

J. Am. Chem. Soc., in press.

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