Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors

α-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α– subunits. Three isoforms (α-BgTx-1–3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (α-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of α-BgTx-1 (LD50 = 0.17–0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve–muscle preparation, α-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. α-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of α-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that α-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α– site as compared with α– ...

Source: Biochemical Journal - April 25, 2019 Category: Biochemistry Authors: Utkin, Y. N., Kuch, U., Kasheverov, I. E., Lebedev, D. S., Cederlund, E., Molles, B. E., Polyak, I., Ivanov, I. A., Prokopev, N. A., Ziganshin, R. H., Jornvall, H., Alvelius, G., Chanhome, L., Warrell, D. A., Mebs, D., Bergman, T., Tsetlin, V. I. Tags: Research Articles Source Type: research