The key to understanding the neurotoxicity of snake bites: why is the mongoose immune to cobra venom (Part 3)

In the final post on the snake venom topic we will discuss how the mongoose has been able to overcome the neurotoxic effects of cobra venom. We have learnt how ACh fits into the shape of the specific shape of the docking pocket in the ACh receptor in the muscle cell membrane (Figure 1).

Figure 1: ACh docks as a key fits a lock in the specifically configured shape of the pocket in the ACh receptor. (click to enlarge)

The cobra makes a neurotoxin that works by blocking the docking  pocket ACh receptor & preventing human or animal ACh from binding with the receptor & thus paralysis ensues. This neurotoxin is a protein, and its many amino acids results in folds & twists producing a protein configuration that resembles 3 fingers & thus its nickname is the “3 finger” protein (Figure 2). Its specific shape fits into various ACh receptors e.g. in man & mice, like a lock into a key.

Figure 2: Cobratoxin with its 3 finger shape which can fit into the pocket of the ACh receptor & block nerve impulses reaching the muscle. (click to enlarge)

In the mongoose the constituent amino acids of the ACh receptor’s binding pocket region differ from those for example in man or a mouse. In position 194, adjacent to the tandem cysteine amino acids is proline amino acid in the toxin binders, whereas in the mongoose it is leucine. This substitution of the amino acid produces a conformational change in ACh pocket, as proline can form a 3-bend or a turn. Such a conformational change does not prevent the Mongoose’s own ACh receptor binding to ACh but it does stop it binding  with much larger polypeptide cobratoxin. In summary the 3 fingered cobratoxin cannot fit into this mongoose receptor i.e. the key does not fit the lock & thus the mongoose (Figure 4) is not paralyzed by cobra venom.

Figure 4: Mongoose, which is resistant to the neurotoxic effects of cape cobra bites. (click to enlarge)

Note we have only discussed neurotoxins in snake venoms. There are other toxins e.g. in puff adders & the boomslang producing cell necrosis, hemolysis, & thrombosis. It appears that some animals e.g. honey badgers, ground squirrels, have immunity to some of these toxins.

How the mongoose can fight the snake: The binding site of the mongoose acetylcholine receptor. Barchan D etal. Proc Natl Acad Sci 89;7717;1992

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