Research Data Leeds Repository
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Molecular dynamics simulations reveal membrane lipid interactions of the full-length lymphocyte specific kinase Lck: dataset
Citation
Prakaash, Dheeraj and Fagnen, Charline and Cook, Graham and Acuto, Oreste and Kalli, Antreas (2022) Molecular dynamics simulations reveal membrane lipid interactions of the full-length lymphocyte specific kinase Lck: dataset. University of Leeds. [Dataset] https://doi.org/10.5518/1158
Dataset description
The membrane-bound lymphocyte-specific protein-tyrosine kinase (Lck) triggers T cell antigen receptor signalling to initiate adaptive immune responses. Despite many structure-function studies, the mode of action of Lck and the potential role of plasma membrane lipids in regulating Lck’s activity remains elusive. Advances in molecular dynamics simulations of membrane proteins in complex lipid bilayers have opened a new perspective in gathering such information. Here, we have modelled the full-length Lck open and closed conformations available from crystallographic studies and simulated its interaction with the inner leaflet of the T cell plasma membrane. In both conformations, we found that the unstructured unique domain and the structured domains including the kinase interacted with the membrane with a preference for PIP lipids. Interestingly, our simulations suggest that the Lck-SH2 domain interacts with lipids differently in the open and closed Lck conformations, demonstrating that lipid interaction can potentially regulate Lck’s conformation and in turn modulate T cell signalling. Additionally, the Lck-SH2 and kinase domain residues that significantly contacted PIP lipids are found to be conserved among the Src family of kinases, thereby potentially representing similar PIP interactions within the family.
| Additional information: | The data was subject to change until the completion of the peer review process. Updates: Charline Fagnen added as author 1 Nov 2022. 15 Nov 2022: Updated versions of CGMD_Lck-SH2.zip CGMD_Lck-SH3.zip CGMD_Lck-SH4U.zip README.txt New files added: CGMD_Lck-FL-closed_without_PIP_lipids.zip and CGMD_Lck-FL-open_without_PIP_lipids.zip | ||||||
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| Keywords: | Full-length Lck, molecular dynamics simulations, protein-lipid interactions, protein conformation | ||||||
| Divisions: | Faculty of Medicine and Health > School of Medicine | ||||||
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| License: | Creative Commons Attribution 4.0 International (CC BY 4.0) | ||||||
| Date deposited: | 24 May 2022 20:08 | ||||||
| URI: | https://archive.researchdata.leeds.ac.uk/id/eprint/968 | ||||||
Files
Documentation
READMEv2.txt [4kB]  |
READMEv2.txt [4kB] 
READMEv2.txt [4kB] Data
All directories for CGMD/ATMD simulations of each protein type [10GB] |
CGMD_Lck-SH2.zip [100MB] |
CGMD_Lck-SH3.zip [101MB] |
CGMD_Lck-SH4U.zip [100MB] |
CGMD_Lck-SH234U.zip [1GB] |
CGMD_Lck-FL-open_without_PIP_lipids.zip [1GB] |
CGMD_Lck-FL-closed_without_PIP_lipids.zip [284MB] |
CGMD_Lck-FL-open.zip [1GB] |
CGMD_Lck-FL-open-mut.zip [1GB] |
CGMD_Lck-FL-closed.zip [815MB] |
ATMD_Lck-FL-open.zip [4GB] |
ATMD_Lck-FL-closed.zip [607MB] |
CGMD_Lck-SH2.zip [100MB]   |
CGMD_Lck-SH3.zip [101MB] |
CGMD_Lck-SH4U.zip [153MB] |