Fasciculins are a class of toxic proteins found in certain snake venoms, notably some species ofmamba. Investigations have revealed distinct forms in somegreen mamba venoms, in particular FAS1 and FAS2[1] Fasciculins are so called because they cause intensefasciculation inmuscle fascicles of susceptible organisms, such as the preferred prey of the snakes. This effect helps to incapacitate the muscles, either killing the prey, or paralysing it so that the snake can swallow it.
The mechanism of action of FAS proteins is associated with attachment to molecules within muscularacetylcholinesterase, and atneuromuscular junctions, thus conferring their ability to interfere withneuromodulatory inhibition.[2]
Fasciculins from mambas inhibit mammalian and fish acetylcholinesterases intensely, but are less active against the correspondingenzymes in insects, reptiles and birds. As one might expect of fast-acting venoms, they are fairly small proteins of about 61 amino acid residues. Their three-dimensional shape is three-fingered, and is secured by four cross-linkingdisulfide bridges.
Venom disrupters ofacetylcholineneurotransmission generally penetrate the neuromuscular junction, where they interfere with either the production or reception of acetylcholine, or thehydrolysis of acetylcholine after it has achieved its function of neurotransmission; mamba fasciculins prevent the final stage of this process by binding to acetylcholinesterase and blocking its action on acetylcholine; the result is that after the acetylcholine has transmitted the required stimulus, it continues with the stimulus after it has become inappropriate.[2] That mechanism is in some ways similar to the effect of the so-calledorganophosphatenerve agents; the blockage of the acetylcholinesterase action is what causes the fasciculation that inspired the namefasciculin.
In mammalian acetylcholinesterase twoconservedperipheral anionic residues form part of the enzyme where the FAS molecule docks. Insect and avian acetylcholinesterases lack the two residues in those positions, and that drastically reduces their affinity for mamba fasciculins. However, there is a significant, though reduced, toxic effect, because severalbasic residues in the venom protein still establish and maintain contacts with the enzyme. This is unusual in protein complementarity, in that it involves attractions between multiple chargedresidues, but without any salt linkage between the molecules.[3]