Protein Interaction Screen on a Peptide Matrix (PrISMa).

Protein-protein interactions (PPI) are essential to understanding the cellular function and key mechanisms necessary for life. Although understanding of the interactome and proteome has exploded due to high-throughput methods in the past decade, often limitations in technical methods result in a partial understanding of all PPI. Here we present a protocol dedicated to the Protein Interaction Screen on a peptide Matrix (PrISMa). PrISMa functions as a high-throughput screen unique to targeting weak and transient interactions often missed in other PPI methods. In addition, PrISMa also excels at the mapping of interactions across linear sequences of proteins that are commonly enriched in intrinsically disordered regions (IDRs) which cover 35-40% of the mammalian proteome. This protocol aims to expand the understanding of the targeted proteins by identifying transient interactors.