On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies
The formation and function of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the r...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/12/1805 |
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| author | Sergey A. Silonov Yakov I. Mokin Eugene M. Nedelyaev Eugene Y. Smirnov Irina M. Kuznetsova Konstantin K. Turoverov Vladimir N. Uversky Alexander V. Fonin |
| author_facet | Sergey A. Silonov Yakov I. Mokin Eugene M. Nedelyaev Eugene Y. Smirnov Irina M. Kuznetsova Konstantin K. Turoverov Vladimir N. Uversky Alexander V. Fonin |
| author_sort | Sergey A. Silonov |
| collection | DOAJ |
| description | The formation and function of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, the maintenance of genome stability, responses to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, the formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML bodies for their tendency for spontaneous liquid–liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. A total of 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs) and the remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SUMOylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected. |
| first_indexed | 2024-03-08T20:58:00Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-08T20:58:00Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-bc77d1db30284ad1a4405b96df5a37b72023-12-22T13:56:11ZengMDPI AGBiomolecules2218-273X2023-12-011312180510.3390/biom13121805On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-BodiesSergey A. Silonov0Yakov I. Mokin1Eugene M. Nedelyaev2Eugene Y. Smirnov3Irina M. Kuznetsova4Konstantin K. Turoverov5Vladimir N. Uversky6Alexander V. Fonin7Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaLaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaLaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaLaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaLaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaLaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaDepartment of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USALaboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, RussiaThe formation and function of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, the maintenance of genome stability, responses to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, the formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML bodies for their tendency for spontaneous liquid–liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. A total of 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs) and the remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SUMOylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected.https://www.mdpi.com/2218-273X/13/12/1805PML bodiesintrinsically disordered proteinsintrinsically disordered regionsliquid–liquid phase separationmembrane-less organellesprotein–protein interactions |
| spellingShingle | Sergey A. Silonov Yakov I. Mokin Eugene M. Nedelyaev Eugene Y. Smirnov Irina M. Kuznetsova Konstantin K. Turoverov Vladimir N. Uversky Alexander V. Fonin On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies Biomolecules PML bodies intrinsically disordered proteins intrinsically disordered regions liquid–liquid phase separation membrane-less organelles protein–protein interactions |
| title | On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies |
| title_full | On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies |
| title_fullStr | On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies |
| title_full_unstemmed | On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies |
| title_short | On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies |
| title_sort | on the prevalence and roles of proteins undergoing liquid liquid phase separation in the biogenesis of pml bodies |
| topic | PML bodies intrinsically disordered proteins intrinsically disordered regions liquid–liquid phase separation membrane-less organelles protein–protein interactions |
| url | https://www.mdpi.com/2218-273X/13/12/1805 |
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