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Alpha-Bungarotoxin 1IDI.png
Schematic diagram of the three-dimensional structure of α-bungarotoxin. Disulfide bonds shown in gold. From PDB: 1IDI​.[1]
OrganismBungarus multicinctus
CAS number11032-79-4

α-Bungarotoxin (α-BTX) is one of the bungarotoxins, components of the venom of the elapid Taiwanese banded krait snake (Bungarus multicinctus). It is a type of α-neurotoxin, a neurotoxic protein that is known to bind competitively and in a relatively irreversible manner to the nicotinic acetylcholine receptor found at the neuromuscular junction, causing paralysis, respiratory failure, and death in the victim.[2] It has also been shown to play an antagonistic role in the binding of the α7 nicotinic acetylcholine receptor in the brain, and as such has numerous applications in neuroscience research.


α-Bungarotoxin is a 74-amino-acid, 8 kDa α-neurotoxin with five disulfide bridges that binds as a competitive antagonist to nicotinic acetylcholine receptors (nAChRs). Like other snake venom α-neurotoxins, it is a member of the three-finger toxin protein family; its tertiary structure consists of a small globular core stabilized by four disulfide bonds, three projecting "finger" loops, and a C-terminal tail. The second loop contains an additional disulfide bond. The tips of fingers I and II form a mobile region that is essential for proper binding.[3]

Hydrogen bonds allow for an antiparallel β-sheet, which keeps the second and third loops roughly parallel. The three-finger structure is preserved by four of the disulfide bridges: the fifth can be reduced without loss to toxicity. The fifth bridge is located on the tip of the second loop.[4]

The multiple disulfide bonds and small amount of secondary structure seen in α-BTX is the cause of the extreme stability of this kind of neurotoxin. Since there are many entropically viable forms of the molecule, it does not denature easily, and has been shown to be resistant to boiling[5] and strong acids.[6][7]


Structure of alpha-bungarotoxin (blue) in complex with the alpha-9 nAChR subunit (orange), showing interactions with loops I and II.[8]

α-neurotoxins antagonistically bind irreversibly 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.[9] The observation that a single molecule of the toxin suffices to inhibit channel opening is in agreement with experimental data on the amount of toxin per receptor.[10] 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]

Research applications

α-Bungarotoxin has played a large role in determining many of the structural details of the nicotinic acetylcholine receptors. It can be conjugated to a fluorophore or enzyme for immunohistochemical staining of fixed tissues and visualization via light or fluorescence microscopy. This application enables morphological characterization of the neuromuscular junctions.[13][14][15]

See also


  1. ^ Zeng H, Moise L, Grant MA, Hawrot E (June 2001). "The solution structure of the complex formed between alpha-bungarotoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica". The Journal of Biological Chemistry. 276 (25): 22930–40. doi:10.1074/jbc.M102300200. PMID 11312275.
  2. ^ Young HS, Herbette LG, Skita V (August 2003). "Alpha-bungarotoxin binding to acetylcholine receptor membranes studied by low angle X-ray diffraction". Biophysical Journal. 85 (2): 943–53. doi:10.1016/s0006-3495(03)74533-0. PMC 1303215. PMID 12885641.
  3. ^ Moise L, Piserchio A, Basus VJ, Hawrot E (April 2002). "NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor". The Journal of Biological Chemistry. 277 (14): 12406–17. doi:10.1074/jbc.M110320200. PMID 11790782.
  4. ^ Love RA, Stroud RM (1986). "The crystal structure of alpha-bungarotoxin at 2.5 A resolution: relation to solution structure and binding to acetylcholine receptor". Protein Engineering. 1 (1): 37–46. doi:10.1093/protein/1.1.37. PMID 3507686.
  5. ^ Tu AT, Hong BS (May 1971). "Purification and chemical studies of a toxin from the venom of Lapemis hardwickii (Hardwick's sea snake)". The Journal of Biological Chemistry. 246 (9): 2772–9. PMID 5554293.
  6. ^ Chicheportiche R, Vincent JP, Kopeyan C, Schweitz H, Lazdunski M (May 1975). "Structure-function relationship in the binding of snake neurotoxins to the torpedo membrane receptor". Biochemistry. 14 (10): 2081–91. doi:10.1021/bi00681a007. PMID 1148159.
  7. ^ Chen YH, Tai JC, Huang WJ, Lai MZ, Hung MC, Lai MD, Yang JT (May 1982). "Role of aromatic residues in the structure-function relationship of alpha-bungarotoxin". Biochemistry. 21 (11): 2592–600. doi:10.1021/bi00540a003. PMID 7093206.
  8. ^ Zouridakis M, Giastas P, Zarkadas E, Chroni-Tzartou D, Bregestovski P, Tzartos SJ (November 2014). "Crystal structures of free and antagonist-bound states of human α9 nicotinic receptor extracellular domain". Nature Structural & Molecular Biology. 21 (11): 976–80. doi:10.1038/nsmb.2900. PMID 25282151.
  9. ^ Young HS, Herbette LG, Skita V (August 2003). "Alpha-bungarotoxin binding to acetylcholine receptor membranes studied by low angle X-ray diffraction". Biophysical Journal. 85 (2): 943–53. doi:10.1016/S0006-3495(03)74533-0. PMC 1303215. PMID 12885641.
  10. ^ Changeux JP, Kasai M, Lee CY (November 1970). "Use of a snake venom toxin to characterize the cholinergic receptor protein". Proceedings of the National Academy of Sciences of the United States of America. 67 (3): 1241–7. doi:10.1073/pnas.67.3.1241. PMC 283343. PMID 5274453.
  11. ^ a b Levitt M, Sander C, Stern PS (February 1985). "Protein normal-mode dynamics: trypsin inhibitor, crambin, ribonuclease and lysozyme". Journal of Molecular Biology. 181 (3): 423–47. doi:10.1016/0022-2836(85)90230-X. PMID 2580101.
  12. ^ Samson AO, Levitt M (April 2008). "Inhibition mechanism of the acetylcholine receptor by alpha-neurotoxins as revealed by normal-mode dynamics". Biochemistry. 47 (13): 4065–70. doi:10.1021/bi702272j. PMC 2750825. PMID 18327915.
  13. ^ Vogel Z, Towbin M, Daniels MP (April 1979). "Alpha-bungarotoxin-horseradish peroxidase conjugate: preparation, properties and utilization for the histochemical detection of acetylcholine receptors". The Journal of Histochemistry and Cytochemistry. 27 (4): 846–51. doi:10.1177/27.4.376692. PMID 376692.
  14. ^ Anderson MJ, Cohen MW (March 1974). "Fluorescent staining of acetylcholine receptors in vertebrate skeletal muscle". The Journal of Physiology. 237 (2): 385–400. doi:10.1113/jphysiol.1974.sp010487. PMC 1350889. PMID 4133039.
  15. ^ Leopoldo M, Lacivita E, Berardi F, Perrone R (July 2009). "Developments in fluorescent probes for receptor research". Drug Discovery Today. 14 (13–14): 706–12. doi:10.1016/j.drudis.2009.03.015. PMID 19573791.

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