Cell Surface β-Lactamase Recruitment: A Facile Selection to Identify Protein-Protein Interactions

Abstract

Protein-protein interactions are central to many cellular processes, and the identification of novel protein-protein interactions is a critical step in the discovery of protein therapeutics. Simple methods to identify naturally existing or laboratory evolved protein-protein interactions are therefore valuable research tools. We have developed a facile selection that links protein-protein interaction-dependent {beta}-lactamase recruitment on the surface of E. coli with resistance to ampicillin. Bacteria displaying a protein which form a complex with a specific protein-{beta}-lactamase fusion are protected from ampicillin-dependent cell death. In contrast, bacteria that do not recruit {beta}-lactamase to the cell surface are killed by ampicillin. Given its simplicity and tunability, we anticipate this selection will be a valuable addition to the palette of methods for illuminating and interrogating protein-protein interactions.