Effects of Acetylation and Phosphorylation on Subunit Interactions in Three Large Eukaryotic Complexes
| Autor: | Nikolina Šoštarić, Vera van Noort, Piero Giansanti, Albert J. R. Heck, Anne-Claude Gavin, Francis J. O’Reilly |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteomics Proteasome Endopeptidase Complex Saccharomyces cerevisiae Proteins Proteome Protein subunit Saccharomyces cerevisiae RNA polymerase II Molecular Dynamics Simulation 01 natural sciences Biochemistry Mass Spectrometry Protein Structure Secondary Analytical Chemistry 03 medical and health sciences 0103 physical sciences Phosphorylation Structural Biology Molecular Biology Acetylation FoldX 010304 chemical physics biology Proteasome Exosome Multienzyme Ribonuclease Complex Tandem Affinity Purification Chemistry Research Computational Biology biology.organism_classification Yeast Exosome Benchmarking 030104 developmental biology Structural biology Binding Affinity biology.protein Biophysics RNA Polymerase II Protein Processing Post-Translational Protein Binding |
| Zdroj: | Molecular and Cellular Proteomics, 17(12), 2387-2401. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Molecular and Cellular Proteomics Molecular and Cellular Proteomics, Vol. 17, No 12 (2018) pp. 2387-2401 |
| ISSN: | 1535-9484 1535-9476 |
| Popis: | Protein post-translational modifications (PTMs) have an indispensable role in living cells as they expand chemical diversity of the proteome, providing a fine regulatory layer that can govern protein-protein interactions in changing environmental conditions. Here we investigated the effects of acetylation and phosphorylation on the stability of subunit interactions in purified Saccharomyces cerevisiae complexes, namely exosome, RNA polymerase II and proteasome. We propose a computational framework that consists of conformational sampling of the complexes by molecular dynamics simulations, followed by Gibbs energy calculation by MM/GBSA. After benchmarking against published tools such as FoldX and Mechismo, we could apply the framework for the first time on large protein assemblies with the aim of predicting the effects of PTMs located on interfaces of subunits on binding stability. We discovered that acetylation predominantly contributes to subunits' interactions in a locally stabilizing manner, while phosphorylation shows the opposite effect. Even though the local binding contributions of PTMs may be predictable to an extent, the long range effects and overall impact on subunits' binding were only captured because of our dynamical approach. Employing the developed, widely applicable workflow on other large systems will shed more light on the roles of PTMs in protein complex formation. ispartof: MOLECULAR & CELLULAR PROTEOMICS vol:17 issue:12 pages:2387-2401 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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