FIGURE 1.

Main classes of direct biosensors for cAMP. A prototypical structure and mechanism of action of unimolecular and multimolecular FRET sensors (A and B respectively), BRET sensors (C), sensors, based on luminescent enzymes (D), and probes operating as conformation-sensitive fluorophores (E), are depicted. All the listed sensors directly bind cAMP molecules and react to binding events with conformational changes that affect their signaling properties—FRET or BRET efficiency (purple arrow), intensity of light production or fluorescence (winding arrows). For more details, please, refer to corresponding sections of the text. Abbreviations: C, PKA catalytic subunit; CFP, cyan fluorescent protein; GRN, green fluorophore; Luc, luciferase; LucN/C, fragments, forming luciferase holoenzyme; R, PKA regulatory subunit; RED, red fluorophore; RP, regulatory protein; YFP, yellow fluorescent protein.