Poneratoxin

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Poneratoxin
SCOP2
1G92 / SCOPe / SUPFAM
OPM superfamily151
OPM protein1g92

Poneratoxin is a paralyzing

voltage gated sodium channels and therefore blocks synaptic transmission in the central nervous system.[1] Specifically, poneratoxin acts on voltage gated sodium channels in skeletal muscle fibers, causing paralysis, and nociceptive fibers, causing pain.[2] It is rated as a 4 plus on the Schmidt sting pain index, the highest possible rating with that system, and its effects can cause waves of pain up to twelve hours after a single sting.[3] It is additionally being studied for its uses in biological insecticides.[4]

Mechanism of action

Schematic shows normal open and inactivated voltage-gated sodium channels on the left. Upon binding of poneratoxin, the sodium channel is forced to stay in the open state, unable to be inactivated. This leads to prolongation of action potentials, which is associated with the pain from bullet ant stings.

Overall, poneratoxin disrupts normal function of

bullet ant stings.[5]

Poneratoxin is in an inactive state when stored in the ant venom reservoir due to the reservoir's acidic conditions, but it becomes toxic when activated via a multistep process. The combination of poneratoxin binding to a cell membrane (in order to act upon a voltage-gated sodium channel) and the movement from acidic conditions in the ant venom reservoir to basic conditions at the target site leads to poneratoxin undergoing a conformational change that activates it.[1]

Catterall et al. hypothesized that some polypeptide neurotoxins that modify voltage-gated channels function via a "voltage-sensor trapping" mechanism. The hypothesis states that neurotoxins similar to poneratoxin, such as alpha-scorpion toxins, act upon sodium channels via binding to the channels' receptor site 3, which normally affects the channels' ability to inactivate. Therefore, receptor site 3 neurotoxins often affect sodium channels by slowing or blocking inactivation.[2][6] Normally, the region of the channel where neurotoxin receptor site 3 is undergoes a conformational change of an outward movement to lead to inactivation. Receptor site 3 neurotoxins are proposed to prevent this conformational change via interaction with acidic and hydrophobic amino acid residues at that site.[6]

When frog

smooth muscles.[8]

Structure

The poneratoxin peptide is stored in an inactive 25-residue peptide (amino acid sequence FLPLLILGSLLMTPPVIQAIHDAQR) in the venom reservoir of

secondary structure is characterized by a helix-turn-helix motif: two alpha helices connected by a beta-turn
.

Poneratoxin inserting into the plasma membrane. Blue regions are hydrophilic, and red regions are hydrophobic

The two

voltage gated sodium channels.[9] Furthermore, the structure of the peptide shifts from a random coil to the structured helix-turn-helix when introduced to a lipid bilayer environment, which indicates that this motif is important for interacting with the membrane.[1]

The two alpha helices, however, have markedly different characteristics. The N-terminal alpha helix is apolar, containing a central

voltage gated sodium channels
.

Toxicology

Many people consider a sting from a

cardiac arrhythmias.[citation needed
]

Toxicity assays have found that the LT50 of poneratoxin, delivered via injections of genetically engineered viruses, to S. frugiperda larvae, was at 131 hours post-injection. A dose of 105 pfu of poneratoxin was sufficient to kill the S. frugiperda larvae, and a dose of 10 ng could paralyze them.[1] Based on these experiments, scientists believe poneratoxin can make a good candidate as a bio-insecticide because of its neurotoxicity to other insects, making it capable of immobilizing or even killing insects infected with it. The making of a recombinant virus by engineering a baculovirus that expresses poneratoxin has been proposed.[1]

See also

References

  1. ^
    PMID 15153103
    .
  2. ^
    S2CID 23620280
    .
  3. ^ Conniff R (2009-08-10). "Oh, Sting, Where Is Thy Death?". newyorktimes.com. Retrieved 26 April 2017.
  4. ^
    PMID 26805882
    .
  5. ^ a b Sullivan, Cody (16 July 2015). "This ant's sting is so bad it feels like getting shot — some call it the worst pain known to man". Business Insider.
  6. ^
    S2CID 5727158
    .
  7. S2CID 166850
    .
  8. PMID 1685425
    .
  9. PMID 9354635
    .
  10. PMID 19837069
    .
  11. ^ Loria K (23 August 2016). "A man who has been stung more than 1,000 times reveals the one bug you really want to avoid". Business Insider.

External links