An improved yeast surface display platform for the screening of nanobody immune libraries

Sci Rep. 2019 Jan 23;9(1):382. doi: 10.1038/s41598-018-37212-3.

Abstract

Fusions to the C-terminal end of the Aga2p mating adhesion of Saccharomyces cerevisiae have been used in many studies for the selection of affinity reagents by yeast display followed by flow cytometric analysis. Here we present an improved yeast display system for the screening of Nanobody immune libraries where we fused the Nanobody to the N-terminal end of Aga2p to avoid steric hindrance between the fused Nanobody and the antigen. Moreover, the display level of a cloned Nanobody on the surface of an individual yeast cell can be monitored through a covalent fluorophore that is attached in a single enzymatic step to an orthogonal acyl carrier protein (ACP). Additionally, the displayed Nanobody can be easily released from the yeast surface and immobilised on solid surfaces for rapid analysis. To prove the generic nature of this novel Nanobody discovery platform, we conveniently selected Nanobodies against three different antigens, including two membrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules* / biosynthesis
  • Cell Adhesion Molecules* / genetics
  • Gene Library*
  • Saccharomyces cerevisiae Proteins* / biosynthesis
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Single-Domain Antibodies* / biosynthesis
  • Single-Domain Antibodies* / genetics

Substances

  • AGA2 protein, S cerevisiae
  • Cell Adhesion Molecules
  • Saccharomyces cerevisiae Proteins
  • Single-Domain Antibodies