vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-38vavilov-4147Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSКомпьютерное моделирование особенностей взаимодействий IL-1 с его рецепторами при шизофренииComputer modeling of the peculiarities in the interaction of IL-1 with its receptors in schizophreniaЧасовскихН. Ю.ChasovskikhN. Yu.

Томск

Tomsk

nch03@mail.ruБобрышеваА. А.BobryshevaA. A.

Томск

Tomsk

ЧижикЕ. Е.ChizhikE. E.

Томск

Tomsk

Сибирский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияSiberian State Medical University of the Ministry of Healthcare of the Russian FederationRussian Federation202430052024283332341Copyright © Часовских Н.Ю., Бобрышева А.А., Чижик Е.Е., 20242024Часовских Н.Ю., Бобрышева А.А., Чижик Е.Е.Chasovskikh N.Y., Bobrysheva A.A., Chizhik E.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4147

Одной из основных теорий развития шизофрении является генетическая, свидетельствующая о вовлечении наследственных факторов в различные процессы, в том числе воспаление. Показано, что воспалительные реакции, протекающие в микроглии, могут влиять на развитие заболевания. Также установлено, что генетически обусловленные изменения IL-1 могут способствовать шизофрении, подтверждая роль кластера генов IL-1 в восприимчивости к болезням. Целью работы была компьютерная оценка структурных взаимодействий белков IL-1 с их рецепторами при шизофрении. Использовалась база данных DisGeNET,  позволяющая оценить достоверность выявленных полиморфизмов IL-1. Проведен поиск полиморфизмов с помощью NCBI PubMed. Сервис NCBI Protein использовался для поиска и анализа положения на хромосоме найденных полиморфизмов. Из базы данных Protein Data Bank были извлечены структуры для проведения моделирования. Моделирование белков выполнялось с помощью сервера SWISS-MODEL, а моделирование белковых взаимодействий – с помощью PRISM. В настоящем исследовании впервые проведено прогнозирование взаимодействий белков IL-1α, IL-1β и IL-1RA с учетом наличия в последовательности соответствующих генов однонуклеотидных полиморфизмов, ассоциированных с шизофренией. Показано, что наличие ассоциированного с шизофренией полиморфизма rs315952 гена белка IL-1RA может привести к ослаблению связи IL-1RA с рецепторами и, предположительно, к запуску сигнального пути IL-1 путем разрыва либо ослабления связи IL-1RA с рецепторами и связыванием IL-1 с ними, что, возможно, вызовет изменение иммунного ответа. Полученные данные вносят теоретический вклад в развитие представлений о молекулярных механизмах влияния наследственных факторов шизофрении на взаимодействия белков семейства IL-1, играющих важную роль в процессах иммунной системы.

One of the primary theories regarding the development of schizophrenia revolves around genetics, indicating the involvement of hereditary factors in various processes, including inflammation. Research has demonstrated that inflammatory reactions occurring in microglia can impact the progression of the disease. It has also been established that genetically determined changes in IL-1 can contribute to schizophrenia, thereby confirming the role of the IL-1 gene cluster in disease susceptibility. The aim of this study is a computer-based assessment of the structural interactions of IL-1 proteins with their receptors in schizophrenia. The study utilized the DisGeNET database, enabling the assessment of the reliability of identified IL-1 polymorphisms. Polymorphisms were also sought using NCBI PubMed. The NCBI Protein service was employed to search for and analyze the position of the identified polymorphisms on the chromosome. Structures for modeling were extracted from the Protein Data Bank database. Protein modeling was conducted using the SWISS-MODEL server, and protein interaction modeling was performed using PRISM. Notably, this study represents the first prediction of the interactions of IL-1α, IL-1β, and IL- 1RA proteins, taking into account the presence of single-nucleotide polymorphisms associated with schizophrenia in the sequence of the corresponding genes. The results indicate that the presence of SNP rs315952 in the IL-1RA protein gene, associated with schizophrenia, may lead to a weakening of the IL-1RA binding to receptors, potentially triggering the initiation of the IL-1 signaling pathway by disrupting or weakening the IL-1RA binding to receptors and facilitating the binding of IL-1 to them. Such alterations could potentially lead to a change in the immune response. The data obtained contribute theoretically to the development of ideas about the molecular mechanisms through which hereditary factors in schizophrenia influence the interactions of proteins of the IL-1 family, which play an important role in the processes of the immune system.

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