Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations
The innate immune system’s natural killer (NK) cells exert their cytolytic function against a variety of pathological challenges, including tumors and virally infected cells. Their activation depends on net signaling mediated via inhibitory and activating receptors that interact with specific ligand...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6670 |
| _version_ | 1797529261671710720 |
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| author | Eva Prašnikar Andrej Perdih Jure Borišek |
| author_facet | Eva Prašnikar Andrej Perdih Jure Borišek |
| author_sort | Eva Prašnikar |
| collection | DOAJ |
| description | The innate immune system’s natural killer (NK) cells exert their cytolytic function against a variety of pathological challenges, including tumors and virally infected cells. Their activation depends on net signaling mediated via inhibitory and activating receptors that interact with specific ligands displayed on the surfaces of target cells. The CD94/NKG2C heterodimer is one of the NK activating receptors and performs its function by interacting with the trimeric ligand comprised of the HLA-E/β2m/nonameric peptide complex. Here, simulations of the all-atom multi-microsecond molecular dynamics in five immune complexes provide atomistic insights into the receptor–ligand molecular recognition, as well as the molecular events that facilitate the NK cell activation. We identify NKG2C, the HLA-E<sub>α2</sub> domain, and the nonameric peptide as the key elements involved in the molecular machinery of signal transduction via an intertwined hydrogen bond network. Overall, the study addresses the complex intricacies that are necessary to understand the mechanisms of the innate immune system. |
| first_indexed | 2024-03-10T10:11:16Z |
| format | Article |
| id | doaj.art-ff0b731fa2c348cbb99a0d8055e13c4a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:11:16Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ff0b731fa2c348cbb99a0d8055e13c4a2023-11-22T01:11:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213667010.3390/ijms22136670Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom SimulationsEva Prašnikar0Andrej Perdih1Jure Borišek2National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaNational Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaNational Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaThe innate immune system’s natural killer (NK) cells exert their cytolytic function against a variety of pathological challenges, including tumors and virally infected cells. Their activation depends on net signaling mediated via inhibitory and activating receptors that interact with specific ligands displayed on the surfaces of target cells. The CD94/NKG2C heterodimer is one of the NK activating receptors and performs its function by interacting with the trimeric ligand comprised of the HLA-E/β2m/nonameric peptide complex. Here, simulations of the all-atom multi-microsecond molecular dynamics in five immune complexes provide atomistic insights into the receptor–ligand molecular recognition, as well as the molecular events that facilitate the NK cell activation. We identify NKG2C, the HLA-E<sub>α2</sub> domain, and the nonameric peptide as the key elements involved in the molecular machinery of signal transduction via an intertwined hydrogen bond network. Overall, the study addresses the complex intricacies that are necessary to understand the mechanisms of the innate immune system.https://www.mdpi.com/1422-0067/22/13/6670immune complexmolecular dynamicsimmunologyNK cellsignal transduction |
| spellingShingle | Eva Prašnikar Andrej Perdih Jure Borišek Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations International Journal of Molecular Sciences immune complex molecular dynamics immunology NK cell signal transduction |
| title | Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations |
| title_full | Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations |
| title_fullStr | Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations |
| title_full_unstemmed | Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations |
| title_short | Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations |
| title_sort | nonameric peptide orchestrates signal transduction in the activating hla e nkg2c cd94 immune complex as revealed by all atom simulations |
| topic | immune complex molecular dynamics immunology NK cell signal transduction |
| url | https://www.mdpi.com/1422-0067/22/13/6670 |
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