Figure 1. Schematic illustration of our concept using yeast cell-surface display technology to selectively track eligible agonistic peptides for human GPCRs by assembling the autonomous signaling complex within individual cells (cell wall trapping of autocrine peptides (CWTrAP) strategy).

The candidate autocrine peptides fused with the anchoring proteins are processed via secretion pathways in engineered yeast cells. Their agonistic activities for heterologously-expressed human GPCRs are discerned on yeast cell membranes. Only when the peptide possesses objective agonistic activity, membrane-peripheral G-proteins promote intracellular signaling and induce transcription of the GFP reporter gene. Because the autocrine peptides are automatically trapped onto individual yeast cell walls, the captured peptides are unable to diffuse toward surrounding yeast cells that express the target human GPCR and any other peptides. T.F. indicates transcription factor.