Biosynthesis
As the DNA sequence for α-LTX is transcribed and translated, an inactive precursor molecule of α-LTX (156.9 kDa) is formed. This precursor molecule undergoes post-translational processing where the eventual, active α-LTX protein (131.5 kDa) is formed.
The N-terminus of the α-LTX precursor molecule is preceded by short hydrophilic sequences ending with a cluster of basic amino acids. These clusters are recognized by proteolytic enzymes (furin-like proteases) which cleave and activate the α-LTX precursor molecules by means of hydrolysis. The C-terminus too is recognized by these furin-like proteases and is also cleaved.
α-LTX precursor molecules are synthesized by free ribosomes in the cytosol and are therefore cytosolic in the secretory epithelial cells of the venom glands., They can, however, associate with secretory granules although they are not taken up in the lumen of the granules. The cytosolic α-LTX precursor molecule is released from the cell by means of holocrine secretion where it ends up in the venom gland of the spider. This gland contains the several proteases involved in the cleavage of the precursor α-LTX molecule.
The α-LTX protein tertiary structure can be divided in three parts: the N-terminal wing (36 kDa), the body (76 kDa), and the C-terminal head (18,5 kDa). Because of C-terminal ankyrin repeats, which mediate protein-protein interactions, the α-LTX monomer forms a dimer with another α-LTX monomer under normal conditions. Tetramer formation activates toxicity.
Read more about this topic: Alpha-Latrotoxin