The correlation between multidomain enzymes and multiple activation mechanisms- The case of phospholipase Cβ and its membrane interactions

Phospholipase C beta 2 (PLC beta 2) 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. PLC beta 2 is activated by G alpha and G beta gamma 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 PLC beta 2-G protein activation and propose a comprehensive model that accounts for both the crystallographic and solution results. (C) 2011 Elsevier B.V. All rights reserved.