A Combinatorial Approach to Engineering a Dual-Specific Metal Switch Antibody

作者：Fanning Sean W; Murtaugh Megan L; Horn James R^*

来源：Biochemistry, 2011, 50(23): 5093-5095.

DOI：10.1021/bi2003845

There is considerable interest in understanding how multiple binding events can be mediated through a single protein interface. Here, a synthetic library approach was developed to generate a novel dual-specific antibody. Using a combinatorial histidine-scanning phage display library, potential metal binding sites were introduced throughout an anti-RNase A antibody interface. Stepwise selection of RNase A and metal binding produced a dual-specific antibody that retained near wild-type affinity for its target antigen while acquiring a competitive metal binding site that is capable of controlling the antibody antigen interaction. Structure analysis of the original antibody RNase A complex suggested peripheral interface residues and loop flexibility are key contributors for obtaining the dual specificity.

• 出版日期2011-6-14