An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation

The enzyme phospholipase C-beta (PLC beta) is a crucial regulator of intracellular calcium levels whose activity is controlled by heptahelical receptors that couple to members of the G(q) family of heterotrimeric G proteins. We have determined atomic structures of two invertebrate homologs of PLC beta (PLC21) from cephalopod retina and identified a helix from the C-terminal regulatory region that interacts with a conserved surface of the catalytic core of the enzyme. Mutations designed to disrupt the analogous interaction in human PLC beta 3 considerably increase basal activity and diminish stimulation by G alpha(q). G alpha(q) binding requires displacement of the autoinhibitory helix from the catalytic core, thus providing an allosteric mechanism for activation of PLC beta.