Decoding protein-peptide interactions using a large, target-agnostic yeast surface display library.

ABSTRACT: Protein-peptide interactions underlie key biological processes and are commonly utilized in biomedical research and therapeutic discovery. It is often desirable to identify peptide sequence properties that confer high-affinity binding to a target protein. However, common approaches to such characterization are typically low throughput and only sample regions of sequence space near an initial hit. To overcome these challenges, we built a yeast surface displayed library representing ~6.1 × 10⁹ unique peptides. We then performed screens against diverse protein targets, including two antibodies, an E3 ubiquitin ligase, and an essential membrane-bound bacterial enzyme. In each case, we observed motifs that appear to drive peptide binding and we identified multiple novel, high-affinit

SUBMITTER: Hurley JD 

PROVIDER: S-EPMC12139779 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature