Year: 2022
Type: preprint
Abstract: Summary PLCβs catalyze the hydrolysis of PIP 2 into IP3 and DAG. PIP 2 regulates the activity of many membrane proteins, while IP3 and DAG lead to increased intracellular Ca 2+ levels and activate PKC, respectively. PLCβs are regulated by GPCRs through direct interaction with Gα q and Gβγ . This study addresses the mechanism by which Gβγ activates PLCβ 3. We show that PLCβ 3 functions as a slow Michaelis-Menten enzyme ( k cat ~2 sec −1 , K M ~0.43 mol %) on membrane surfaces. Its partition coefficient ( K x ~2.9 * 10 4 ) is such that only a small quantity of PLCβ 3 exists in the membrane in the absence of Gβγ . When Gβγ is present, equilibrium binding ( K eq ~0.009 mol %) increases PLCβ 3 in the membrane, increasing V max in proportion. Atomic structures on membrane vesicle surfaces show that two Gβγ anchor PLCβ 3 with its catalytic site oriented toward the membrane surface. This principle of activation explains rapid stimulated catalysis with low background catalysis.
Authors: Maria E. Falzone, Roderick MacKinnon
Institutions: Howard Hughes Medical Institute, Rockefeller University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4313457115