Kappa-bungarotoxin
| Kappa-bungarotoxin | |
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The three-dimensional structure of α-bungarotoxin, highlighting disulfide bonds, from PDB: 1KBA.[1]
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| Identifiers | |
| Organism | |
| 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[edit]
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[disambiguation needed] 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[edit]
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[edit]
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[edit]
- ^ a b 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.
- ^ a b 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.
- ^ a b 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 3794919
. PMID 24130909. - ^ a b 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.
- ^ a b 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.
- ^ 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.
