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Simulation data from the publication "Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme"
Citation
Le Huray, Kyle I. P. (2022) Simulation data from the publication "Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme". University of Leeds. [Dataset] https://doi.org/10.5518/1133
Dataset description
A repository of simulation data from the publication "Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme". PLCγ enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCg require understanding of an active, membrane bound form, that can hydrolyse inositol-lipid substrates. Here we demonstrate that PLCγ1 cannot bind membranes unless the autoinhibition is disrupted. Through extensive MD simulations and experimental evidence, we characterise membrane binding by the catalytic core domains and reveal novel sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLCγ1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCγ1 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention. This dataset contains:
- DATASET1: coarse-grained MD simulation data for the binding of the WT PLCγ1 core domains to a model membrane
- DATASET 2: coarse-grained MD simulation data for the binding of a mutant (clone E) variant of the PLCγ1 core domains to a model membrane
- DATASET 3: coarse-grained MD simulation data for the binding of the SH3 domain of PLCγ1 to a model membrane
- DATASET 4: coarse-grained MD simulation data for the binding of the tandem nSH2-cSH3 domains of PLCγ1 to a model membrane
- DATASET 5: coarse-grained MD simulation data for the binding of the sPH domain of PLCγ1 to a model membrane
- DATASET 6: atomistic MD simulation data of the membrane bound state of the wild-type (WT) core domains
| Keywords: | molecular dynamics simulations, phospholipase c, membrane proteins, biochemistry, biophysics, computational biochemistry | ||||||
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| Subjects: | C000 - Biological sciences > C700 - Molecular biology, biophysics & biochemistry | ||||||
| Divisions: | Faculty of Biological Sciences > Astbury Centre for Structural Molecular Biology Faculty of Biological Sciences > School of Molecular and Cellular Biology |
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| License: | Creative Commons Attribution 4.0 International (CC BY 4.0) | ||||||
| Date deposited: | 16 Jun 2022 20:08 | ||||||
| URI: | https://archive.researchdata.leeds.ac.uk/id/eprint/986 | ||||||
Files
Documentation
readme.txt [4kB]  |
readme.txt [4kB] 
readme.txt [4kB] Data
dataset_1_core_WT_CG_simulations.zip [15GB] |
dataset_2_core_cloneE_CG_simulations.zip [15GB] |
dataset_3_spPH_CG_simulations.zip [1GB] |
dataset_4_nSH2_cSH2_CG_simulations.zip [1GB] |
dataset_5_SH3_CG_simulations.zip [1GB] |
dataset_6_atomistic_md_simulations.zip [9GB] |