α-Neurotoxin

Add links
Source: Wikipedia, the free encyclopedia.
disulfide bonds. From PDB: 1IDI​.[1]

α-Neurotoxins are a group of neurotoxic

Hydrophiidae. They can cause paralysis, respiratory failure, and death. Members of the three-finger toxin protein family, they are antagonists of post-synaptic nicotinic acetylcholine receptors (nAChRs) in the neuromuscular synapse that bind competitively and irreversibly, preventing synaptic acetylcholine (ACh) from opening the ion channel. Over 100 α-neurotoxins have been identified and sequenced.[2]

History

The term α-neurotoxin was coined by

bungarotoxin with the α- prefix because it happened to be slowest moving of the bungarotoxins under starch zone electrophoresis.[3] The "α-" prefix subsequently came to connote any toxins with postsynaptic action. Members of this group are sometimes referred to as "curaremimetics" due to the similarity of their effects with the plant alkaloid curare.[4][5]

As more snake venoms were characterized, many were found to contain homologous nAChR-antagonist proteins. These came to be collectively known as the snake venom α-neurotoxins.[5]

General structure

All α-neurotoxins share the

disulfide bonds, three loops or "fingers", and a C-terminal tail.[4]
The class can be divided into two groups distinguished by length; short-chain neurotoxins have 60-62 residues and only the four core disulfide bonds characteristic of the fold, while long-chain neurotoxins have 66 or more residues, often including a longer
α-cobratoxin are both long-type.[6]

Functions

For specifics, see α-Bungarotoxin and nicotinic acetylcholine receptor

α-Neurotoxins antagonistically bind tightly and noncovalently to nAChRs of skeletal muscles, thereby blocking the action of ACh at the postsynaptic membrane, inhibiting ion flow and leading to paralysis. nAChRs contain two binding sites for snake venom neurotoxins. Some computational studies of the mechanism of inhibition using normal mode dynamics[11] suggest that a twist-like motion caused by ACh binding may be responsible for pore opening, and that this motion is inhibited by toxin binding.[11][12]

Evolution

Although three-finger protein domains are widespread, three-finger toxins appear only in snakes, and are particularly enriched in

positive selection,[14] possibly due to an evolutionary arms race with prey species.[15]

Snake nAchRs have specific sequence features that render them poor binding partners for alpha-neurotoxins.

domestic pig, and hedgehog lineages replace aromatic amino acids with charged residues; at least in some lineages, these molecular adaptations likely reflect predation on venomous snakes.[18][16]

References

  1. PMID 11312275
    .
  2. S2CID 20158638
    .
  3. S2CID 84443027
    .
  4. ^
    PMID 20670641
    .
  5. ^
    PMID 23416229
    .
  6. ^
    PMID 11790782
    .
  7. PMID 10491072
    .
  8. PMID 8555211
    .
  9. PMID 7721859
    .
  10. S2CID 4638613
    .
  11. ^
    PMID 2580101
    .
  12. PMID 18327915
    .
  13. PMID 28326549
    .
  14. PMID 24253238
    .
  15. PMID 23219381
    .
  16. ^
    S2CID 11196041
    .
  17. PMID 2780569
    .
  18. ^
    PMID 25796346
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Α-Neurotoxin&oldid=1177113681"