Research Data Leeds Repository

Simulation data from the publication "Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme"

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
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
Related resources:	Location Type https://www.doi.org/10.1126/sciadv.abp9688 Publication
License:	Creative Commons Attribution 4.0 International (CC BY 4.0)
Date deposited:	16 Jun 2022 20:08
URI:	http://archive.researchdata.leeds.ac.uk/id/eprint/986
Additional details Additional details Creators: Creators ORCID Other ID Email Primary affiliation Primary affiliation ID Primary affiliation ID type Secondary affiliation Secondary affiliation ID Secondary affiliation ID type Le Huray, Kyle I.P. https://orcid.org/0000-0002-7518-5666 University Of Leeds https://ror.org/024mrxd33 ROR Type of data: Dataset Research funders: BBSRC Grant numbers: BB/M011151/1 Publication date: 2022 Data collection method: Molecular dynamics simulations Resource language: English Research project title: White Rose Doctoral Training Partnership in Mechanistic Biology and its Strategic Application Publisher: University of Leeds Contact Email Address: A.Kalli@leeds.ac.uk Last Modified: 20 Jun 2022 07:19

Files

Documentation

readme.txt [4kB] readme.txt [4kB] readme.txt [4kB] Visible to: Anyone File name: readme.txt Content type: Documentation Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 4kB

Data

dataset_1_core_WT_CG_simulations.zip [15GB] dataset_1_core_WT_CG_simulations.zip [15GB] dataset_1_core_WT_CG_simulations.zip [15GB] Visible to: Anyone File name: dataset_1_core_WT_CG_simulations.zip Content type: Data Description: Coarse-grained molecular dynamics simulation of membrane binding by the wild-type (WT) core domains of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 15GB

dataset_2_core_cloneE_CG_simulations.zip [15GB] dataset_2_core_cloneE_CG_simulations.zip [15GB] dataset_2_core_cloneE_CG_simulations.zip [15GB] Visible to: Anyone File name: dataset_2_core_cloneE_CG_simulations.zip Content type: Data Description: Coarse-grained molecular dynamics simulation of membrane binding by the mutant clone E variant of the core domains of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 15GB

dataset_3_spPH_CG_simulations.zip [1GB] dataset_3_spPH_CG_simulations.zip [1GB] dataset_3_spPH_CG_simulations.zip [1GB] Visible to: Anyone File name: dataset_3_spPH_CG_simulations.zip Content type: Data Description: Coarse-grained molecular dynamics simulation of membrane binding by the SH3 domain of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 1GB

dataset_4_nSH2_cSH2_CG_simulations.zip [1GB] dataset_4_nSH2_cSH2_CG_simulations.zip [1GB] dataset_4_nSH2_cSH2_CG_simulations.zip [1GB] Visible to: Anyone File name: dataset_4_nSH2_cSH2_CG_simulations.zip Content type: Data Description: Coarse-grained molecular dynamics simulation of membrane binding by the tandem nSH2-cSH2 domains of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 1GB

dataset_5_SH3_CG_simulations.zip [1GB] dataset_5_SH3_CG_simulations.zip [1GB] dataset_5_SH3_CG_simulations.zip [1GB] Visible to: Anyone File name: dataset_5_SH3_CG_simulations.zip Content type: Data Description: Coarse-grained molecular dynamics simulation of membrane binding by the sPH domain of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 1GB

dataset_6_atomistic_md_simulations.zip [9GB] dataset_6_atomistic_md_simulations.zip [9GB] dataset_6_atomistic_md_simulations.zip [9GB] Visible to: Anyone File name: dataset_6_atomistic_md_simulations.zip Content type: Data Description: Atomistic molecular dynamics simulation of membrane bound state of the wild-type (WT) core domains of phospholipase Cγ1 Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 9GB