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Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptorsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 11 ноября 2019 г.
- Авторы: Utkin Yuri N., Kuch Ulrich, Kasheverov Igor E., Lebedev Dmitry S., Cederlund Ella, Molles Brian E., Polyak Iakov, Ivanov Igor A., Prokopev Nikita A., Ziganshin Rustam H., Jornvall Hans, Alvelius Gunvor, Chanhome Lawan, Warrell David A., Mebs Dietrich, Bergman Tomas, Tsetlin Victor I.
- Журнал: Biochemical Journal
- Том: 476
- Номер: 8
- Год издания: 2019
- Издательство: Portland Press, Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 1285
- Последняя страница: 1302
- DOI: 10.1042/bcj20180909
- Аннотация: alpha delta-Bungarotoxins, a novel group of long-chain alpha-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 alpha-delta subunits. Three isoforms (alpha delta-BgTx-1-3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (alpha delta-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to alpha-bungarotoxin (alpha-BgTx), a classical blocker of muscle-type and neuronal alpha 7, alpha 8, and alpha 9 alpha 10 nAChRs. The toxicity of alpha delta-BgTx-1 (LD50 = 0.17-0.28 mu g/g mouse, i.p. injection) is essentially as high as that of alpha-BgTx. In the chick biventer cervicis nerve-muscle preparation, alpha delta-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by alpha-BgTx, acetylcholine response was fully reversible by washing. alpha delta-BgTxs, similar to alpha-BgTx, bind with high affinity to alpha 7 and muscle-type nAChRs. However, the major difference of alpha delta-BgTxs from alpha-BgTx and other naturally occurring alpha-neurotoxins is that alpha delta-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 alpha-delta site as compared with alpha-epsilon or alpha-gamma binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in alpha delta-BgTxs. Thus, alpha delta-BgTxs are new tools for studies on nAChRs.
- Добавил в систему: Смирнова Инна Григорьевна