PIONEER: A periplasmic display platform for synthetic biology-based screening of genetically encoded protein regulators.

ABSTRACT: Periplasmic display in yeast is a promising but underdeveloped method for screening and studying genetically encoded biomolecules. We present Periplasmic dIsplay Of geNetically Encoded rEgulatoRs (PIONEER), a modular platform that localizes peptides, proteins, and nanobodies to the membrane-proximal periplasmic space of Saccharomycescerevisiae, enabling direct interrogation of membrane protein function. By optimizing secretion signals (ss) and display scaffolds, PIONEER ensures stable ligand retention and robust autocrine signaling. The ability to assess peptide and protein ligand activity through signaling, rather than binding alone, marks a key advance toward function-first screening. Applied to human G protein-coupled receptors, the system enables detection of surface expression, ligand

SUBMITTER: Rowe JB 

PROVIDER: S-EPMC12796099 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature