Weinstein Harel, Scarlata Suzanne
Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
Biochim Biophys Acta. 2011 Dec;1808(12):2940-7. doi: 10.1016/j.bbamem.2011.08.028. Epub 2011 Aug 30.
Phospholipase Cβ2 (PLCβ2) is a large, multidomain enzyme that catalyzes the hydrolysis of the signaling lipid phosphoinositol 4,5 bisphosphate (PIP2) to promote mitogenic and proliferative changes in the cell. PLCβ2 is activated by Gα and Gβγ subunits of heterotrimeric G proteins, as well as small G proteins and specific peptides. Activation depends on the nature of the membrane surface. Recent crystal structures suggest one model of activation involving the movement of a small autoinhibitory loop upon membrane binding of the enzyme. Additionally, solution studies indicate multiple levels of activation that involve changes in the membrane orientation as well as interdomain movement. Here, we review the wealth of biochemical studies of PLCβ2-G protein activation and propose a comprehensive model that accounts for both the crystallographic and solution results.
磷脂酶Cβ2（PLCβ2）是一种大型多结构域酶，它催化信号脂质磷脂酰肌醇4,5-二磷酸（PIP2）的水解，以促进细胞中的促有丝分裂和增殖变化。PLCβ2由异源三聚体G蛋白的Gα和Gβγ亚基以及小G蛋白和特定肽激活。激活取决于膜表面的性质。最近的晶体结构提出了一种激活模型，该模型涉及酶与膜结合后一个小的自抑制环的移动。此外，溶液研究表明存在多个激活水平，涉及膜取向的变化以及结构域间的移动。在这里，我们综述了大量关于PLCβ2 - G蛋白激活的生化研究，并提出了一个综合模型，该模型兼顾了晶体学和溶液研究结果。
