To activate a G protein coupled receptor permanently by cell surface photodynamic action

Unlike agonist-stimulated receptor activation, 1O2 activates GPCR cholecystokinin 1 (CCK1R) in type II photodynamic action, with soluble photosensitizers SALPC (675 nm) or protein photosensitizers (KillerRed, 585 nm; miniSOG 450 nm), together with a pulse of light. Three lines of evidence shed light on the mechanism of GPCR activated by singlet oxygen (GPCR-ABSO): 1/ CCK1R is quantitatively converted from dimer to monomer; 2/ TM3, a pharmacophore for photodynamic CCK1R activation, can be transplanted to non-susceptible M3R; 3/ Larger size of disordered region in ICL3 correlates with higher sensitivity to photodynamic CCK1R activation. GPCR-ABSO will add to the arsenal of designer GPCR such as RASSL and DREADD, but show some clear advantages: enhanced selectivity, long-lasting activation with no need for repeated drug administration, antagonist-binding site remains intact when needed, ease to apply to multiple GPCR. This type of permanent photodynamic activation may be applied to functional proteins other than GPCR.