vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-78-3S-3vestnik-bio-msu-1267Research ArticleКРАТКИЕ СООБЩЕНИЯSHORT COMMUNICATIONSСхемы замыкания дисульфидных связей в токсинах пауков семейства Ctenidae. Сравнение с предсказаниями нейросети AlphaFold 2.0Disulfide bond patterns in the toxins of spiders of the Ctenidae family. Comparison with AlphaFold 2.0 predictionshttps://orcid.org/0000-0002-7884-3257МироновП. А.MironovP. A.

Миронов Павел Андреевич – тех.-лаб. лаборатории структурной биологии ионных каналов

г. Москва, 117997, ул. Миклухо-Маклая, д. 16/10

Тел: 8-495-335-01-00

Miklukho-Maklaya 16/10, 117997, Moscow

mironov@nmr.ruhttps://orcid.org/0000-0003-1383-3522ШенкаревЗ. О.ShenkarevZ. O.

Шенкарев Захар Олегович – докт. физ.-мат. наук, гл. науч. сотр. лаборатории структурной биологии ионных каналов

г. Москва, 117997, ул. Миклухо-Маклая, д. 16/10

Тел: 8-495-335-01-00

Miklukho-Maklaya 16/10, 117997, Moscow

zakharshenkarev@yandex.ruИнститут биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова, Российская академия наукРоссияShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesRussian Federation202330112023783S1320Copyright © Миронов П.А., Шенкарев З.О., 20232023Миронов П.А., Шенкарев З.О.Mironov P.A., Shenkarev Z.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1267

Пауки блуждающие, или пауки-бегуны (Ctenidae), имеют многокомпонентные яды, в которых идентифицировано более 500 различных пептидов и белков, названных ктенитоксинами. Основными компонентами яда являются цистеин-богатые пептиды, содержащие мотив ингибиторного цистинового узла (inhibitor cystine knot, ICK). Фармакологическое разнообразие ктенитоксинов позволяет рассматривать некоторые из них как прообразы для создания новых лекарств для лечения хронической боли, болезни Хантингтона, эректильной дисфункции и глаукомы. По расположению остатков цистеина в аминокислотной последовательности ктенитоксины разделяют на 14 групп, содержащих от шести до 14 остатков Cys. В настоящее время определена пространственная структура только одного ктенитоксина ω-CNTX-Pn4a (Phα1β или Tx3-6) бразильского странствующего паука Phoneutria nigriventer. Еще 10 структурных групп ктенитоксинов имеют гомологию с известными пространственными структурами токсинов пауков других семейств и других белков, а для трех групп структурные гомологи неизвестны. В данной работе предложены возможные схемы формирования дисульфидных связей для всех групп ктенитоксинов. Сравнение полученных схем с предсказаниями программы AlphaFold 2.0 показывает, что эта нейронная сеть не всегда корректно предсказывает структуры цистеин-богатых пептидов, особенно если моделируются структуры зрелых молекул без лидерных последовательностей.

Wandering spiders (family Ctenidae) have multicomponent venoms in which more than 500 different peptides and proteins, called ctenitoxins, have been identified. The main components of the venom are cysteine-rich peptides containing an inhibitory cystine knot (ICK) motif. The pharmacological diversity of ctenitoxins allows us to consider some of them as prototypes for the development of new drugs for the treatment of chronic pain, Huntington’s disease, erectile dysfunction and glaucoma. According to the location of cysteine residues in the amino acid sequence, ctenitoxins are divided into 14 groups containing from 6 to 14 Cys residues. Currently, the spatial structure of only one ctenitoxin, ω-CNTX-Pn4a (Pha1β or Tx3-6) from the Brazilian wandering spider Phoneutria nigriventer, has been determined. Another 10 structural groups of ctenitoxins have homology with the known spatial structures of spider toxins of other families and other proteins, and for three groups the structural homologues are unknown. In this paper, we proposed possible disulfide bonding patterns for all groups of ctenitoxins. A comparison of the obtained schemes with the predictions of the AlphaFold 2.0 program shows that this neural network does not always correctly predict the structures of cysteine-rich peptides, especially if the structures of mature molecules without leader sequences are modeled.

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The authors declare that there are no conflicts of interest present.