A universal peptide matrix interactomics approach to disclose motif-dependent protein binding

Evelyn Ramberger, Lorena Suarez-Artiles, Daniel Perez-Hernandez, Mohamed Haji, Oliver Popp, Ulf Reimer, Achim Leutz*, Gunnar Dittmar, Philipp Mertins

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)


Protein-protein interactions mediated by intrinsically disordered regions are often based on short linear motifs (SLiMs). SLiMs are implicated in signal transduction and gene regulation yet remain technically laborious and notoriously challenging to study. Here, we present an optimized method for a protein interaction screen on a peptide matrix (PRISMA) in combination with quantitative MS. The protocol was benchmarked with previously described SLiM-based protein-protein interactions using peptides derived from EGFR, SOS1, GLUT1, and CEBPB and extended to map binding partners of kinase activation loops. The detailed protocol provides practical considerations for setting up a PRISMA screen and subsequently implementing PRISMA on a liquid-handling robotic platform as a cost-effective high-throughput method. Optimized PRISMA can be universally applied to systematically study SLiM-based interactions and associated post-translational modifications or mutations to advance our understanding of the largely uncharacterized interactomes of intrinsically disordered protein regions.

Original languageEnglish
Article number100135
JournalMolecular and Cellular Proteomics
Early online date13 Aug 2021
Publication statusPublished - 2021


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