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Yeast surface display for screening combinatorial polypeptide libraries


Display on the yeast cell wall is well suited for engineering mammalian cell-surface and secreted proteins (e.g., antibodies, receptors, cytokines) that require endoplasmic reticulum-specif ic post-translational processing for efficient folding and activity. C-terminal fusion to the Aga2p mating adhesion receptor of Saccharomyces cerevisiae has been used for the selection of scFv antibody fragments with threefold decreased antigen dissociation rate from a randomly mutated library. A eukaryotic host should alleviate expression biases present in bacterially propagated combinatorial libraries. Quantitative flow cytometric analysis enables fine discrimination of kinetic parameters for protein binding to soluble ligands.

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Correspondence to K. Dane Wittrup.

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Boder, E., Wittrup, K. Yeast surface display for screening combinatorial polypeptide libraries. Nat Biotechnol 15, 553–557 (1997).

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