FIGURE 9.

Schematic illustration of calpain binding and cleavage of NCX1. Calpain binds to NCX1-CLD (amino acids 345–373) and NCX1-CBD1 (amino acids 411–439) through its catalytic domain (amino acids 269–304 in domain II) and domain III (amino acids 413–448), respectively. When calpain is activated, it cleaves NCX1-Met³⁶⁹, leading to inhibition of NCX1. After cleavage, calpain dissociates from NCX1. Recent evidence suggests that mammalian NCX1 may have 10 TM domains similar to NCX_Mj from archaebacterial Methanococcus jannaschii (52).