Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer

Abstract Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongl...

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Autores principales:	Dmitry Tikhonov, Liudmila Kulikova, Arthur T. Kopylov, Vladimir Rudnev, Alexander Stepanov, Kristina Malsagova, Alexander Izotov, Dmitry Kulikov, Alexey Zulkarnaev, Dmitry Enikeev, Natalia Potoldykova, Anna L. Kaysheva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69d55964673c4c3ba2e81ab07faa771f
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spelling	oai:doaj.org-article:69d55964673c4c3ba2e81ab07faa771f2021-12-02T18:51:28ZProteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer10.1038/s41598-021-98201-72045-2322https://doaj.org/article/69d55964673c4c3ba2e81ab07faa771f2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98201-7https://doaj.org/toc/2045-2322Abstract Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational fluctuations are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.Dmitry TikhonovLiudmila KulikovaArthur T. KopylovVladimir RudnevAlexander StepanovKristina MalsagovaAlexander IzotovDmitry KulikovAlexey ZulkarnaevDmitry EnikeevNatalia PotoldykovaAnna L. KayshevaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dmitry Tikhonov Liudmila Kulikova Arthur T. Kopylov Vladimir Rudnev Alexander Stepanov Kristina Malsagova Alexander Izotov Dmitry Kulikov Alexey Zulkarnaev Dmitry Enikeev Natalia Potoldykova Anna L. Kaysheva Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
description	Abstract Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational fluctuations are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
format	article
author	Dmitry Tikhonov Liudmila Kulikova Arthur T. Kopylov Vladimir Rudnev Alexander Stepanov Kristina Malsagova Alexander Izotov Dmitry Kulikov Alexey Zulkarnaev Dmitry Enikeev Natalia Potoldykova Anna L. Kaysheva
author_facet	Dmitry Tikhonov Liudmila Kulikova Arthur T. Kopylov Vladimir Rudnev Alexander Stepanov Kristina Malsagova Alexander Izotov Dmitry Kulikov Alexey Zulkarnaev Dmitry Enikeev Natalia Potoldykova Anna L. Kaysheva
author_sort	Dmitry Tikhonov
title	Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
title_short	Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
title_full	Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
title_fullStr	Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
title_full_unstemmed	Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer
title_sort	proteomic and molecular dynamic investigations of ptm-induced structural fluctuations in breast and ovarian cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69d55964673c4c3ba2e81ab07faa771f
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Proteomic and molecular dynamic investigations of PTM-induced structural fluctuations in breast and ovarian cancer

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