2 research outputs found
Imaging GPCR Dimerization in Living Cells with Cucurbit[7]uril and Hemicyanine as a āTurn-Onā Fluorescence Probe
Although
multiple forms of dimers have been described for GPCR,
their dynamics and function are still controversially discussed field.
Fluorescence microscopy allows GPCR to be imaged within their native
context; however, a key challenge is to site-specifically incorporate
reporter moieties that can produce high-quality signals upon formation
of GPCR dimers. To this end, we propose a supramolecular sensor approach
to detect agonist-induced dimer formation of Ī¼-opioid receptors
(Ī¼ORs) at the surface of intact cells. With the macrocyclic
host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer
strands directed against the histidine residues, the sensing module
is assembled by hostāguest complexation once the histidine-tagged
Ī¼ORs dimerize and bring the discrete supramolecular units into
close proximity. With the enhanced sensitivity attributed by the āturn-onā
fluorescence emission and high specificity afforded by the intermolecular
recognition, in situ visualization of dynamic GPCR dimerization was
realized with high precision, thereby validating the supramolecular
sensing entity as a sophisticated and versatile strategy to investigate
GPCR dimers, which represent an obvious therapeutic target