Interactions of Nucleosomes with Acidic Patch-Binding Peptides: A Combined Structural Bioinformatics, Molecular Modeling, Fluorescence Polarization, and Single-Molecule FRET Study

Oleinikov, P.D.; Fedulova, A.S.; Armeev, G.A.; Motorin, N.A.; Singh-Palchevskaia, L.; Sivkina, A.L.; Feskin, P.G.; Glukhov, G.S.; Afonin, D.A.; Komarova, G.A.; Kirpichnikov, M.P.; Studitsky, V.M.; Feofanov, A.V.; Shaytan, A.K.

Авторы: Oleinikov Pavel D., Fedulova Anastasiia S., Armeev Grigoriy A., Motorin Nikita A., Singh-Palchevskaia Lovepreet, Sivkina Anastasiia L., Feskin Pavel G., Glukhov Grigory S., Afonin Dmitry A., Komarova Galina A., Kirpichnikov Mikhail P., Studitsky Vasily M., Feofanov Alexey V., Shaytan Alexey K.
Журнал: International Journal of Molecular Sciences
Том: 24
Номер: 20
Год издания: 2023
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 15194
Последняя страница: 15194
DOI: 10.3390/ijms242015194
Аннотация: In eukaryotic organisms, genomic DNA associates with histone proteins to form nucleosomes. Nucleosomes provide a basis for genome compaction, epigenetic markup, and mediate interactions of nuclear proteins with their target DNA loci. A negatively charged (acidic) patch located on the H2A-H2B histone dimer is a characteristic feature of the nucleosomal surface. The acidic patch is a common site in the attachment of various chromatin proteins, including viral ones. Acidic patch-binding peptides present perspective compounds that can be used to modulate chromatin functioning by disrupting interactions of nucleosomes with natural proteins or alternatively targeting artificial moieties to the nucleosomes, which may be beneficial for the development of new therapeutics. In this work, we used several computational and experimental techniques to improve our understanding of how peptides may bind to the acidic patch and what are the consequences of their binding. Through extensive analysis of the PDB database, histone sequence analysis, and molecular dynamic simulations, we elucidated common binding patterns and key interactions that stabilize peptide–nucleosome complexes. Through MD simulations and FRET measurements, we characterized changes in nucleosome dynamics conferred by peptide binding. Using fluorescence polarization and gel electrophoresis, we evaluated the affinity and specificity of the LANA1-22 peptide to DNA and nucleosomes. Taken together, our study provides new insights into the different patterns of intermolecular interactions that can be employed by natural and designed peptides to bind to nucleosomes, and the effects of peptide binding on nucleosome dynamics and stability.
Добавил в систему: Олейников Павел Денисович

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Interactions of Nucleosomes with Acidic Patch-Binding Peptides: A Combined Structural Bioinformatics, Molecular Modeling, Fluorescence Polarization, and Single-Molecule FRET Studyстатья

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