Fig. 5: Schematic model of α-LTX activation, tetrameric prepore assembly, and transition to a cation permeable channel.
From: Structural basis of α-latrotoxin transition to a cation-selective pore
The precursor of α-LTX is activated by proteolytic cleavage of its inhibitory terminal domains in the venom gland. Tetramerization, a prerequisite for pore formation, may be enhanced through association with presynaptic receptors. A central Ca2+ binding site brings the HBD domains into close proximity. The C-terminal helices of the HBDs, along with the CD domains, reorient to form a tetrameric coiled-coil stalk. The N-terminal helices of this stalk, stabilized by disulfide bridges, insert into the membrane, forming a cation-permeable transmembrane channel.
