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.
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 and strong acids.
Structure of alpha-bungarotoxin (blue) in complex with the alpha-9 nAChR subunit (orange), showing interactions with loops I and II.
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. 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. Some computational studies of the mechanism of inhibition using normal mode dynamics 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.
^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. PMID11312275.
^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. PMID11790782.
^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. PMID3507686.
^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. PMID5554293.
^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. PMID1148159.
^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. PMID7093206.
^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. PMID25282151.
^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. PMID376692.