Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane
The gamma-hemolysin protein is one of the most common pore-forming toxins expressed by the pathogenic bacterium <i>Staphylococcus aureus</i>. The toxin is used by the pathogen to escape the immune system of the host organism, by assembling into octameric transmembrane pores on the surfac...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/8/7113 |
| _version_ | 1797605190029803520 |
|---|---|
| author | Costanza Paternoster Thomas Tarenzi Raffaello Potestio Gianluca Lattanzi |
| author_facet | Costanza Paternoster Thomas Tarenzi Raffaello Potestio Gianluca Lattanzi |
| author_sort | Costanza Paternoster |
| collection | DOAJ |
| description | The gamma-hemolysin protein is one of the most common pore-forming toxins expressed by the pathogenic bacterium <i>Staphylococcus aureus</i>. The toxin is used by the pathogen to escape the immune system of the host organism, by assembling into octameric transmembrane pores on the surface of the target immune cell and leading to its death by leakage or apoptosis. Despite the high potential risks associated with <i>Staphylococcus aureus</i> infections and the urgent need for new treatments, several aspects of the pore-formation process from gamma-hemolysin are still unclear. These include the identification of the interactions between the individual monomers that lead to the formation of a dimer on the cell membrane, which represents the unit for further oligomerization. Here, we employed a combination of all-atom explicit solvent molecular dynamics simulations and protein–protein docking to determine the stabilizing contacts that guide the formation of a functional dimer. The simulations and the molecular modeling reveal the importance of the flexibility of specific protein domains, in particular the N-terminus, to drive the formation of the correct dimerization interface through functional contacts between the monomers. The results obtained are compared with the experimental data available in the literature. |
| first_indexed | 2024-03-11T04:57:36Z |
| format | Article |
| id | doaj.art-ea570316d2f447ca88fb1541dc320761 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:57:36Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea570316d2f447ca88fb1541dc3207612023-11-17T19:35:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248711310.3390/ijms24087113Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model MembraneCostanza Paternoster0Thomas Tarenzi1Raffaello Potestio2Gianluca Lattanzi3Department of Physics, University of Trento, Via Sommarive 14, I-38123 Trento, ItalyDepartment of Physics, University of Trento, Via Sommarive 14, I-38123 Trento, ItalyDepartment of Physics, University of Trento, Via Sommarive 14, I-38123 Trento, ItalyDepartment of Physics, University of Trento, Via Sommarive 14, I-38123 Trento, ItalyThe gamma-hemolysin protein is one of the most common pore-forming toxins expressed by the pathogenic bacterium <i>Staphylococcus aureus</i>. The toxin is used by the pathogen to escape the immune system of the host organism, by assembling into octameric transmembrane pores on the surface of the target immune cell and leading to its death by leakage or apoptosis. Despite the high potential risks associated with <i>Staphylococcus aureus</i> infections and the urgent need for new treatments, several aspects of the pore-formation process from gamma-hemolysin are still unclear. These include the identification of the interactions between the individual monomers that lead to the formation of a dimer on the cell membrane, which represents the unit for further oligomerization. Here, we employed a combination of all-atom explicit solvent molecular dynamics simulations and protein–protein docking to determine the stabilizing contacts that guide the formation of a functional dimer. The simulations and the molecular modeling reveal the importance of the flexibility of specific protein domains, in particular the N-terminus, to drive the formation of the correct dimerization interface through functional contacts between the monomers. The results obtained are compared with the experimental data available in the literature.https://www.mdpi.com/1422-0067/24/8/7113gamma-hemolysinpore-forming toxinsmembrane proteinsmolecular dynamics |
| spellingShingle | Costanza Paternoster Thomas Tarenzi Raffaello Potestio Gianluca Lattanzi Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane International Journal of Molecular Sciences gamma-hemolysin pore-forming toxins membrane proteins molecular dynamics |
| title | Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane |
| title_full | Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane |
| title_fullStr | Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane |
| title_full_unstemmed | Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane |
| title_short | Gamma-Hemolysin Components: Computational Strategies for LukF-Hlg2 Dimer Reconstruction on a Model Membrane |
| title_sort | gamma hemolysin components computational strategies for lukf hlg2 dimer reconstruction on a model membrane |
| topic | gamma-hemolysin pore-forming toxins membrane proteins molecular dynamics |
| url | https://www.mdpi.com/1422-0067/24/8/7113 |
| work_keys_str_mv | AT costanzapaternoster gammahemolysincomponentscomputationalstrategiesforlukfhlg2dimerreconstructiononamodelmembrane AT thomastarenzi gammahemolysincomponentscomputationalstrategiesforlukfhlg2dimerreconstructiononamodelmembrane AT raffaellopotestio gammahemolysincomponentscomputationalstrategiesforlukfhlg2dimerreconstructiononamodelmembrane AT gianlucalattanzi gammahemolysincomponentscomputationalstrategiesforlukfhlg2dimerreconstructiononamodelmembrane |