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Interactions of nucleosomes with acidic patch binding peptides: Combining structural analysis, MD simulations, and experimentsстатья Тезисы
Дата последнего поиска статьи во внешних источниках: 17 апреля 2024 г.
- Авторы: Shaytan Alexey, Armeev Grigoriy A., Oleinikov Pavel D., Motorin Nikita A., Singh-Palchevskaya Lavprit, Sivkina Anastasiia L., Feskin Pavel G., Komarova Galina A., Kirpichnikov Mikhail P., Feofanov Alexei V., Afonin Dmitry A., Fedulova Anastasiia S., Studitsky Vasily M., Glukhov Grigory S.
- Журнал: Biophysical Journal
- Том: 123
- Номер: 3, Supplement 1
- Год издания: 2024
- Издательство: Biophysical Society
- Местоположение издательства: United States
- Первая страница: 3a
- DOI: 10.1016/j.bpj.2023.11.150
- Аннотация: A negatively charged patch is a characteristic feature of the nucleosomal surface. It is located mainly on the H2A-H2B histone dimer and is a common siteused by different proteins to attach to nucleosomes, including host chromatin proteins and viral proteins. Peptides that bind to the acidic patch are perspective moieties that can be used to modulate epigenetic mechanisms of genomefunctioning, disrupt interactions of nucleosomes with viral proteins, or used totarget protein or chemical moieties to the nucleosomes. In this talk I’ll presentour work, where we used various in silico and experimental approaches toenhance our understanding of how peptides may bind to the acidic patchand how their binding may influence nucleosome stability, geometry, and interactions. We performed a comprehensive analysis of the PDB database andcharacterized the geometry and composition of the common protein motifsinvolved in nucleosome binding. Molecular dynamics simulations and analysis of histone sequence variants was further used to elucidated key interactions that stabilize peptides on the nucleosome. Through MD simulationsand FRET measurements, we further analyzed changes conferred by peptidebinding to the nucleosome dynamics. Fluorescence polarization and gel-electrophoresis experiments were used to assess the affinity and specificityof a few peptides with respect to DNA and nucleosome binding. Takentogether we have obtained new insights into the different patterns of intermolecular interactions employed by natural peptides to bind to nucleosomes, andformulated strategies for designing artificial peptides with tuneable nucleosome binding properties. This research was supported by the RSF grant#19-74-30003.
- Добавил в систему: Армеев Григорий Алексеевич