Fig. 5: Schematic for RhoA-mediated PLCε activation.
From: RhoA allosterically activates phospholipase Cε via its EF hands
Under basal conditions, PLCε is autoinhibited by the X–Y linker in the cytoplasm. RhoA is activated downstream of G12/13-coupled receptors by a RhoA guanine nucleotide exchange factor (RhoGEF). The activated G protein binds the lipase via the E2α′ helix, which, together with the PLCε CDC25, PH, and TIM barrel domains, may define a common membrane interaction surface. RhoA binding induces conformational changes within the lipase, moving the EF hands closer to the TIM barrel domain, stabilizing the EF1/2-EF3/4 interface and the CDC25-PH domain module closer to the TIM barrel. These long-range conformational changes may facilitate displacement of the X–Y linker from the active site, exposing the active site once at the membrane. The RhoA·GTP–PLCε PH-C reconstruction is shown in the boxed inset. The prenylated C-tail of RhoA is shown as a dashed line, and together with the TIM barrel and PH domain, may form a shared membrane interaction surface. The ends of the PLCε X–Y linker are indicated by hot pink asterisks.
