A Tethered Yeast Surface Display System Facilitates Enriching Epitope-Specific Binding Interactions

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ID: 321491
2026
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Abstract
Engineering proteins for therapeutic applications is a field that has seen substantial growth in the past two decades, but challenges remain. A major deficiency in current strategies is the lack of a means to efficiently screen for binding to key epitopes to yield a desired function. To meet this challenge, we designed a tethered yeast surface display construct that leverages high local concentrations by tethering a candidate protein binder to a target protein of interest (POI) via a flexible peptide linker. These high local concentrations enable screening of epitope-specific binders based on decreased signal due to inhibitory function when the construct is assayed alongside a competitive POI binder. We demonstrate that epitope-specific screening and enrichment is possible based on fluorescent output and study key optimization parameters. We anticipate this technique will accelerate binder development by reducing the need for downstream low throughput epitope mapping of isolated proteins.
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Authors Rojhae A. Panton, Jakob Lind, Amanda Richardson, Isabela Panozzo, Daniela Gómez García, Syed Muzaffar, Lawrence A. Stern
Journal Protein Engineering Design and Selection
Year 2026
DOI
10.1093/protein/gzag019
URL
https://doi.org/10.1093/protein/gzag019
Keywords Keywords not found

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