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Oligomerization analysis as a tool to elucidate the mechanism of EBV latent membrane protein 1 inhibition by pentamidineстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 23 января 2026 г.
- Авторы: Kot Erik F., Wang Yibo, Goncharuk Sergey A., Zhang Bo, Arseniev Alexander S., Wang Xiaohui, Mineev Konstantin S.
- Журнал: Biochimica et Biophysica Acta - Biomembranes
- Том: 1862
- Номер: 10
- Год издания: 2020
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Номер статьи: 183380
- DOI: 10.1016/j.bbamem.2020.183380
- Аннотация: Latent membrane protein 1 (LMP1) is a gene product of the Epstein-Barr virus (EBV), a widely spread virus present in 90–95% of the world's population. EBV can lead to several malignancies, in which LMP1 was shown to play a key role. LMP1 is active only in the oligomeric form and its fifth transmembrane domain (TMD-5) is critical for the oligomerization, with D150 identified as a key residue for LMP1 activation. Here we propose an NMR-based approach to treat the complex oligomerization equilibria with slow conformational exchange. Using this method we investigate the TMD-5 in DPC micelles. We show that the pKa of D150 equals 7.4. Uncharged form of TMD-5associates into dimers and trimers, deprotonation of D150 induces the high-order oligomerization of the protein and enhances dramatically its trimerization. Pentamidine interacts mainly with the charged TMD 5, destroying the oligomers and stabilizing the monomer and trimer. Using computer simulations we investigate the structural basis of TMD-5/pentamidine interaction. Our data suggest that D150 is likely charged in the full length LMP1 under native conditions
- Добавил в систему: Кот Эрик Федорович