Analysis of surface displayed
scFv- and GFP-202–08 fusions.
(a) Surface display levels of unfused, wild-type intein fused or 202–08
intein fused scFvs and GFP were analyzed by flow cytometry. The MFI
of the FLAG-positive yeast populations was quantified, and all were
normalized to the 4–4–20 construct containing the wild-type
intein. Reported are the means ± SD of three independent yeast
transformants. Statistical analysis was performed by an unpaired Student’s t-test (*p < 0.05; **p < 0.01; NS, not significant p > 0.05). (b)
ScFv
and GFP per molecule activity was evaluated by detecting binding to
the scFv antigens at saturating ligand concentrations or by measuring
GFP fluorescence. Activity per molecule was determined by calculating
the ratio of the geometric means for activity (binding or fluorescence)
to FLAG expression levels and normalizing to the unfused construct
lacking intein. Plotted are the means ± SD from three independent
yeast transformants, with statistical significance determined by an
unpaired Student’s t-test (*p < 0.05; **p < 0.01; NS, not significant p > 0.05) (c) For intein-mediated protein release, MESNA
reacts to release the scFv or GFP from the display construct and append
a carboxy-terminal thioester. For EPL functionalization, the carboxy-terminal
thioester reacts with a biotinylated peptide containing an amino-terminal
cysteine to covalently link the scFv or GFP to the biotin by an amide
bond. (d) Products of the reaction depicted in panel c resolved and
analyzed by Western blotting to detect release of the scFv or GFP
(∼30 kDa) from the 202–08 intein construct using an
anti-FLAG antibody (F) or biotin functionalization via EPL with an
anti-biotin antibody (B). A small amount of uncleaved scFv-intein-Aga2p
product can be seen in the anti-FLAG Western blot between ∼80
kDa and 100 kDa due to the glycosylation of Aga2p.