Phospholipase C (PLC) enzymes hydrolyze phosphoinositide lipids to inositol phosphates and diacylglycerol. Direct activation of PLCβ by Gα_q and/or Gβγ subunits mediates signaling by Gq and some Gi coupled G-protein-coupled receptors (GPCRs), respectively. PLCβ isoforms contain a unique C-terminal extension, consisting of proximal and distal C-terminal domains (CTDs) separated by a flexible linker. The structure of PLCβ3 bound to Gα_q is known, however, for both Gα_q and Gβγ; the mechanism for PLCβ activation on membranes is unknown. We examined PLCβ2 dynamics on membranes using hydrogen-deuterium exchange mass spectrometry (HDX-MS). Gβγ caused a robust increase in dynamics of the distal C-terminal domain (CTD). Gα_q showed decreased deuterium incorporation at the Gα_q binding site on PLCβ. In vitro Gβγ-dependent activation of PLC is inhibited by the distal CTD. The results suggest that disruption of autoinhibitory interactions with the CTD leads to increased PLCβ hydrolase activity.

磷脂酶C（PLC）酶将磷酸肌醇脂质水解为肌醇磷酸酯和二酰基甘油。通过GαPLCβ的直接活化_q和/或Gβγ亚单位介导通过Gq和一些GI信令耦合G蛋白偶联受体（GPCR），分别。PLCβ亚型包含一个独特的C端延伸区，该延伸区由通过柔性接头分隔的近端和远端C端域（CTD）组成。PLCβ3的结构结合到Gα _q然而已知，对于同Gα _q和Gβγ; 膜上PLCβ激活的机制尚不清楚。我们使用氢-氘交换质谱（HDX-MS）检查了膜上PLCβ2的动力学。Gβγ导致远端C末端结构域（CTD）的动力学强劲增加。Gα _q表明在Gα减少的氘掺入_q上PLCβ结合位点。体外CTD抑制PLC的Gβγ依赖性激活。结果表明，与CTD的自抑制相互作用的破坏导致PLCβ水解酶活性增加。