Regulation of PIEZO force sensitivity by inter-blade handshaking

A repository of simulation data from the publication “Regulation of PIEZO1 channel force sensitivity by inter-blade handshaking”. PIEZOs form trimeric calcium-permeable non-selective cationic channels that serve mechanical sensing needs across eukaryotic biology. Forces act on the channels by causing their curved blades to flatten and decompact, leading to an activated state, but it is unclear how this might be regulated to enable the channels to adapt to different contexts. To identify potential mechanisms, we performed coarse-grained and all-atom molecular dynamics simulations on human PIEZO1 channel. We observed an inter-blade handshake interaction mediated by basic amino acid residues in two flexible helices that coordinate with the regulated anionic lipid phosphatidylinositol 4,5-bisphosphate. In silico mutation of phosphatidylinositol 4,5-bisphosphate sites on the handshake short helix, referred to as SHM PIEZO1, destabilised the inter-blade handshake interaction. The interaction determined the resting configuration of the channel, blade curvature, compactness and ion pore structure. This dataset contains: -Dataset 1: Coarse-grained MD simulation data for the wildtype human PIEZO1 simulated in an endothelial membrane containing 5% PIP2. -Dataset 2: Coarse-grained MD simulation data for the wildtype human PIEZO1 simulated in an endothelial membrane containing 0% PIP2. -Dataset 3: Coarse-grained MD simulation data for the SHM PIEZO1 simulated in an endothelial membrane containing 5% PIP2. -Dataset 4: All-atom MD simulation data for the WT PIEZO1 simulated in an endothelial membrane containing 5% PIP2 without applied tension (+1 bar) and with applied tension (-30 bar). -Dataset 5: All-atom MD simulation data for the SHM PIEZO1 simulated in an endothelial membrane containing 5% PIP2 without applied tension (+1 bar) and with applied tension (-30 bar).