Fluorophore-linked immunoassay for detecting
azF-CCR site-specifically
peptide epitope modified by SpAAC. (A) Scheme showing the in-culture
labeling of the GPCR, CCR5, the uaa azF genetically encoded at a target
site. SpAAC reaction is used to site-specifically attach the FLAG
peptide epitope (green) conjugated to a DBCO (red) via a maleimide
cross-linker (DBCO-FLAG). (B) Representative results of the on-cell
ISA for measuring the FLAG signal with or without DBCO. HEK293T cells
expressing N24azF or F96azF CCR5 variants were treated with 100 μM
DBCO-FLAG (dark gray bars), and data for the untreated cells are also
shown (light gray bars). Wild-type CCR5 (wt) and mock-transfected
(MT) controls were tested under the same condition. Error bars represent
the standard error of the mean of triplicate measurements. (C) Western
blot analysis of labeled and purified azF-CCR5. In the left panel,
the crude lysate sample was probed simultaneously with anti-FLAG polyclonal
antibody and 1D4 monoclonal antibody to detect the extent of FLAG
peptide epitope tagging (green) and full-length receptor expression
(red), respectively. The receptor is visualized in the red channel
and separates at 37 kDa. The right panel shows full-length CCR5 immunoaffinity
purified with the C-terminal 1D4 engineered tag. The purified receptor
separates at 37 kDa (red) as detected with the anti-1D4 antibody against
the C-terminal 1D4 epitope tag, and the FLAG tag is visualized with
the anti-FLAG pAb (green).