“Weak Toxin” from Naja kaouthia Is a Nontoxic Antagonist of α7 and Muscle-type Nicotinic Acetylcholine Receptors

• Published in: The Journal of biological chemistry 2001-05, Vol.276 (19), p.15810
• Main Authors: Yuri N. Utkin, Viktoriya V. Kukhtina, Elena V. Kryukova, Florence Chiodini, Daniel Bertrand, Christoph Methfessel, Victor I. Tsetlin
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M100788200

A novel “weak toxin” (WTX) from Naja kaouthia snake venom competes with [ 125 I]α-bungarotoxin for binding to the membrane-bound Torpedo californica acetylcholine receptor (AChR), with an IC 50 of ∼2.2 μ m . In this respect, it is ∼300 times less potent than neurotoxin II from Naja oxiana and α-cobratoxin from N. kaouthia , representing short-type and long-type α-neurotoxins, respectively. WTX and α-cobratoxin displaced [ 125 I]α-bungarotoxin from the Escherichia coli -expressed fusion protein containing the rat α7 AChR N-terminal domain 1–208 preceded by glutathione S -transferase with IC 50 values of 4.3 and 9.1 μ m , respectively, whereas for neurotoxin II the IC 50 value was >100 μ m . Micromolar concentrations of WTX inhibited acetylcholine-activated currents in Xenopus oocyte-expressed rat muscle AChR and human and rat α7 AChRs, inhibiting the latter most efficiently (IC 50 of ∼8.3 μ m ). Thus, a virtually nontoxic “three-fingered” protein WTX, although differing from α-neurotoxins by an additional disulfide in the N-terminal loop, can be classified as a weak α-neurotoxin. It differs from the short chain α-neurotoxins, which potently block the muscle-type but not the α7 AChRs, and is closer to the long α-neurotoxins, which have comparable potency against the above-mentioned AChR types.