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. 2024 Mar 29;14(4):417. doi: 10.3390/biom14040417

Figure 2.

Figure 2

Optical methods for ORAI1 channel modulating. (A) Directly interfering with ORAI1 channels by blue light. By introducing mutations and inserting the LOV2 domain between TM2 and TM3, a light-operated calcium channel (LOCa) was generated, inducing calcium entry upon blue light illumination. (B) Schematic diagram showing the activation mechanism of femtoSOC. With the stimulation of femtosecond laser pulses, photoexcited flavins are linked to cysteine residues in ORAI1 via thioether bonds, thereby inducing ORAI1 channel opening and calcium influx. (C) Graphical illustration of photocrosslinking-induced ORAI1 activation. The photocrosslinking unnatural amino acids (UAAs), p-azido-L-phenylalanine (Azi) and p-benzoyl-L-phenylalanine (Bpa), were introduced into the ORAI1 peptide chain through genetic code expansion technology. These UAAs respond to UV light illumination and control the state of ORAI1 channels. (D) The photochemical regulation of ORAI1 channels. The small-molecule inhibitor 2-aminoethoxydiphenyl borate (2-APB) was fused with the photoswitching molecule azobenzene to create light-operated CRAC channel inhibitors (LOCIs). CRAC small-molecule inhibitors were fused with azopyrazole to develop photoswitchable CRAC channel inhibitors (piCRACs). Both LOCI and piCRAC affect the activation of ORAI channels. PM: plasma membrane.