FIGURE 1.

Domain structure of TRPM2 [after (46)] and location of the two nucleotide binding sites in the cryoEM structure of human TRPM2 [pdb: 6PUS, (48)]: the recently identified N-terminal binding site between the MHR1 and MHR2 domains (blue) and the established C-terminal binding site in the NudT9H domain. The insets show the different conformation of ADPR in the binding sites as determined from the cryoEM structure, the ADPR in the N-terminal binding site assumes a horseshoe like conformation whereas the ADPR in in the NudT9H domain has a more elongated conformation. The depicted ADPR molecules have been reoriented relative to the TRPM2 structure to better illustrate the difference in conformation between the two binding sites. In a structure that has been solved in the presence of 8-Br-cADPR, 8-Br-cADPR occupies the N-terminal binding site between MHR1/MHR2 (48).