Kappa-bungarotoxin

Kappa-bungarotoxin

The three-dimensional structure of α-bungarotoxin, highlighting disulfide bonds, from PDB: 1KBA​.[1]
Identifiers
Organism Bungarus multicinctus
Symbol N/A
UniProt P01398

Kappa-bungarotoxin (often written κ-Bgt; historically also called toxin F[2]) is a protein neurotoxin of the bungarotoxin family that is found in the venom of the many-banded krait, a snake found in Taiwan. Kappa-bungarotoxin is a high affinity antagonist of nicotinic acetylcholine receptors (nAChRs), particularly of CHRNA3; it causes a post-synaptic blockade of neurotransmission. Although there is significant variability in the clinical effects of snake bites, neuromuscular paralysis and respiratory failure are associated with krait bites.[3]

Discovery

Kappa-bungarotoxin was first reported in 1983 as a component of the venom of Bungarus multicinctus that differed in biological effect from the previously known alpha-bungarotoxin: Kappa, but not alpha, was capable of impeding nicotinic signaling in the chick ciliary ganglion. The newly discovered toxin was designated "kappa" as an allusion to the Latin word kiliaris ("from the eye"), also the root of "ciliary".[4] Separately identified toxins designated "toxin F" and "bungarotoxin 3.1" were identified by protein sequencing as identical to kappa-bungarotoxin.[2]

Mechanism and biological effects

Kappa-bungarotoxin binds to the nicotinic acetylcholine receptors of the skeletal muscles, predominantly to the nicotinic receptor subunit alpha 3 (CHRNA3) and to a lesser extent alpha 4. Two distinct binding surfaces, both on the N-terminal extracellular face of the receptor subunit, have been identified.[5]

Kappa-bungarotoxin is a receptor antagonist, meaning it blocks the normal response of the receptor to acetylcholine, which inhibits neurotransmission and therefore causes neuromuscular paralysis. Like the alpha-bungarotoxins, kappa-bungarotoxin causes a post-synaptic blockade of signaling; this is in contrast to the beta-bungarotoxins which induce a pre-synaptic block.[3] The distinction between the effects of alpha and kappa was first identified functionally, as differences in effects on specific neural structures.[4][6] The basis of this functional difference has been molecularly characterized as differences in receptor subtype specificity; the pentameric receptors are assembled from different distributions of subunits in neurons and in muscles.[5]

Structure

The kappa-bungarotoxin polypeptide is 66 amino acids long and folds into an antiparallel beta sheet structure stabilized by five conserved disulfide bonds, a structural feature shared by many peptide toxins. Unlike other members of the bungarotoxin family, kappa is a dimer.[1]

References

  1. 1 2 Dewan, JC; Grant, GA; Sacchettini, JC (8 November 1994). "Crystal structure of kappa-bungarotoxin at 2.3-A resolution.". Biochemistry. 33 (44): 13147–54. doi:10.1021/bi00248a026. PMID 7947721.
  2. 1 2 Loring, RH; Andrews, D; Lane, W; Zigmond, RE (15 October 1986). "Amino acid sequence of toxin F, a snake venom toxin that blocks neuronal nicotinic receptors.". Brain Research. 385 (1): 30–7. doi:10.1016/0006-8993(86)91543-x. PMID 3021284.
  3. 1 2 Ranawaka, UK; Lalloo, DG; de Silva, HJ (2013). "Neurotoxicity in snakebite--the limits of our knowledge.". PLoS neglected tropical diseases. 7 (10): e2302. doi:10.1371/journal.pntd.0002302. PMC 3794919Freely accessible. PMID 24130909.
  4. 1 2 Chiappinelli, VA (24 October 1983). "Kappa-bungarotoxin: a probe for the neuronal nicotinic receptor in the avian ciliary ganglion.". Brain Research. 277 (1): 9–22. doi:10.1016/0006-8993(83)90902-2. PMID 6139146.
  5. 1 2 Chiappinelli, VA; Weaver, WR; McLane, KE; Conti-Fine, BM; Fiordalisi, JJ; Grant, GA (1996). "Binding of native kappa-neurotoxins and site-directed mutants to nicotinic acetylcholine receptors.". Toxicon. 34 (11-12): 1243–56. doi:10.1016/s0041-0101(96)00110-9. PMID 9027980.
  6. ↑ Dryer, SE; Chiappinelli, VA (19 December 1983). "Kappa-bungarotoxin: an intracellular study demonstrating blockade of neuronal nicotinic receptors by a snake neurotoxin.". Brain Research. 289 (1-2): 317–21. doi:10.1016/0006-8993(83)90033-1. PMID 6318897.
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