Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study
The translocator protein (TSPO) is a transmembrane protein present across the three domains of life. Its functional quaternary structure consists of one or more subunits. In mice, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of m...
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4299 |
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| author | Zeineb Si Chaib Alessandro Marchetto Klevia Dishnica Paolo Carloni Alejandro Giorgetti Giulia Rossetti |
| author_facet | Zeineb Si Chaib Alessandro Marchetto Klevia Dishnica Paolo Carloni Alejandro Giorgetti Giulia Rossetti |
| author_sort | Zeineb Si Chaib |
| collection | DOAJ |
| description | The translocator protein (TSPO) is a transmembrane protein present across the three domains of life. Its functional quaternary structure consists of one or more subunits. In mice, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the <i>mouse</i> protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the <i>mouse</i> protein. |
| first_indexed | 2024-03-10T16:12:48Z |
| format | Article |
| id | doaj.art-9d8a182e920142a5b0088daf8689d600 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:12:48Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9d8a182e920142a5b0088daf8689d6002023-11-20T14:20:10ZengMDPI AGMolecules1420-30492020-09-012518429910.3390/molecules25184299Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation StudyZeineb Si Chaib0Alessandro Marchetto1Klevia Dishnica2Paolo Carloni3Alejandro Giorgetti4Giulia Rossetti5Institute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, 52425 Jülich, GermanyDepartment of Biotechnology, University of Verona, 37134 Verona, ItalyInstitute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, 52425 Jülich, GermanyThe translocator protein (TSPO) is a transmembrane protein present across the three domains of life. Its functional quaternary structure consists of one or more subunits. In mice, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the <i>mouse</i> protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the <i>mouse</i> protein.https://www.mdpi.com/1420-3049/25/18/4299TSPOMartini force-fieldcholesterol |
| spellingShingle | Zeineb Si Chaib Alessandro Marchetto Klevia Dishnica Paolo Carloni Alejandro Giorgetti Giulia Rossetti Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study Molecules TSPO Martini force-field cholesterol |
| title | Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study |
| title_full | Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study |
| title_fullStr | Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study |
| title_full_unstemmed | Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study |
| title_short | Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study |
| title_sort | impact of cholesterol on the stability of monomeric and dimeric forms of the translocator protein tspo a molecular simulation study |
| topic | TSPO Martini force-field cholesterol |
| url | https://www.mdpi.com/1420-3049/25/18/4299 |
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