Life Sciences Institute, Department of Biophysics, University of Michigan, Ann Arbor, Michigan, USA.
Nat Struct Mol Biol. 2011 Aug 7;18(9):999-1005. doi: 10.1038/nsmb.2095.
The enzyme phospholipase C-β (PLCβ) is a crucial regulator of intracellular calcium levels whose activity is controlled by heptahelical receptors that couple to members of the Gq family of heterotrimeric G proteins. We have determined atomic structures of two invertebrate homologs of PLCβ (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 PLCβ3 considerably increase basal activity and diminish stimulation by Gαq. Gαq binding requires displacement of the autoinhibitory helix from the catalytic core, thus providing an allosteric mechanism for activation of PLCβ.
酶磷脂酶 C-β（PLCβ）是细胞内钙离子水平的关键调节剂，其活性受与 Gq 家族异源三聚体 G 蛋白成员偶联的七螺旋受体控制。我们已经确定了来自头足类动物视网膜的 PLCβ 的两种无脊椎动物同源物（PLC21）的原子结构，并鉴定了来自 C 端调节区的一个螺旋，该螺旋与酶的催化核心的保守表面相互作用。设计用于破坏人 PLCβ3 中类似相互作用的突变会显著增加基础活性并减少 Gαq 的刺激。Gαq 结合需要将自抑制螺旋从催化核心中置换出来，从而为 PLCβ 的激活提供了变构机制。
