A phage-based system to select multiple protein-protein interactions simultaneously from combinatorial libraries

Selectively infective phage (SIP) can be used to identify protein-protein i nteractions. SIP was modified to facilitate the simultaneous selection of i nteracting protein pairs from large combinatorial libraries. An interferenc e-resistant phage mas constructed which non-covalently, but stably links th e genetic information of an interacting pair, encoded separately on phage a nd phagemid vectors, by co-packaging into hetero-polyphages. In a model sys tem, the interaction between a SIP-selected peptide and the intracellular d omain of the p75 neurotrophin receptor was detected in the presence of a 10 (4)-fold excess of a non-interacting control pair (jun leucine zipper and p 75 intracellular domain) via SIP hetero-polyphage transductants. To minimiz e the redundancy of transductants and to minimize possible ligand exchange generated in a solution-based SIP screening, a filter-based in situ infecti vity screening aas developed, The combination of the above techniques may p rovide a powerful system for rapid screening of very large sequence spaces. (C) 1998 Federation of European Biochemical Societies.