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

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

本数据集源自发表于论文《磷脂酶Cγ的膜相互作用表征揭示活性酶的关键特征》（"Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme"）的模拟数据。磷脂酶Cγ（phospholipase Cγ, PLCγ）在静息细胞中处于自抑制状态，是细胞内信号转导通路的关键组成部分，同时与疾病发生发展密切相关。要阐明PLCγ的生理激活与异常激活机制，必须先明确其活性膜结合形式——该形式可水解肌醇脂质底物（inositol-lipid substrates）。本研究证实，若不解除自抑制状态，PLCγ1无法结合细胞膜。通过大量分子动力学（molecular dynamics, MD）模拟与实验证据，我们对催化核心结构域的膜结合特性进行了系统表征，并揭示了全新的脂质相互作用位点。所鉴定的位点具有协同效应，且与自抑制界面重叠，同时被证实对细胞内的磷脂酶活性至关重要。本研究直接证明，PLCγ1通过调控区域阻塞其膜结合表面实现自抑制，而激活过程必须使PLCγ1转变为具备膜结合能力的构象。对关键膜相互作用位点的认知，进一步拓展了关于其激活、失调及治疗干预的机制框架。

本数据集包含以下内容：
- DATASET1：野生型（wild-type, WT）PLCγ1核心结构域与模型膜结合的粗粒度分子动力学模拟数据
- DATASET 2：PLCγ1核心结构域突变体（克隆E）与模型膜结合的粗粒度分子动力学模拟数据
- DATASET 3：PLCγ1的SH3结构域（Src Homology 3 domain, SH3）与模型膜结合的粗粒度分子动力学模拟数据
- DATASET 4：PLCγ1的串联nSH2-cSH3结构域与模型膜结合的粗粒度分子动力学模拟数据
- DATASET 5：PLCγ1的sPH结构域（sPH domain）与模型膜结合的粗粒度分子动力学模拟数据
- DATASET 6：野生型（WT）核心结构域膜结合状态的全原子分子动力学模拟数据