Methionine gamma lyase fused with S3 domain VGF forms octamers and adheres to tumor cells via binding to EGFR

Methods for targeting enzymes exhibiting anticancer properties, such as methionine γ-lyase (MGL), have not yet been sufficiently developed. Here, we present the data describing the physico-chemical properties and cytotoxic effect of fusion protein MGL-S3 ― MGL from Clostridium sporogenes translationally fused to S3 domain of the viral growth factor of smallpox. MGL-S3 has methioninase activity comparable to native MGL. In solution, MGL-S3 protein primarily forms octamers, whereas native MGL, on the contrary, usually forms tetramers. MGL-S3 binds to the surface of the neuroblastoma SH-SY5Y and epidermoid carcinoma A431 cells and, unlike native MGL, remains there and retains its cytotoxic effect after media removal. In HEK293T cells lacking EGFRs, no adhesion was recorded. Confocal fluorescence microscopy confirms the preferential adhesion of MGL-S3 to tumor cells, while it avoids getting into lysosomes. Both MGL and MGL-S3 arrest cell cycle of SH-SY5Y cells mainly in the G1 phase, while only MGL-S3 retains this ability after washing the cells.

Авторы
Bondarev N.A.1 , Bagaeva D.F.1 , Bazhenov S.V.1 , Buben M.M.1 , Bulushova N.V.2 , Ryzhykau Yu.L.1, 3 , Okhrimenko I.S.1 , Zagryadskaya Yu.A.1 , Maslov I.V.1 , Anisimova N.Yu. 4, 5 , Sokolova D.V. 4, 5, 6 , Kuklin A.I.1, 3 , Pokrovsky V.S. 4, 5, 6 , Manukhov I.V.1
Язык
Английский
Страницы
149319
Статус
Опубликовано
Том
691
Год
2024
Организации
  • 1 Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia
  • 2 National Research Center Kurchatov Institute, Kurchatov Genomic Center, Moscow, 123182, Russia
  • 3 Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980, Dubna, Russia
  • 4 Department of Biochemistry, Patrice Lumumba People's Friendship University (RUDN University), Moscow, 117198, Russia
  • 5 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, 115478, Russia
  • 6 Center of Life Sciences, Sirius University of Science and Technology, Sochi, 354340, Russia
Дата создания
28.01.2024
Дата изменения
28.01.2024
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/106158/
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