8EMV

Phospholipase C beta 3 (PLCb3) in solution

Summary for 8EMV

• Entry DOI: 10.2210/pdb8emv/pdb
• Related: 8EMW 8EMX
• EMDB information: 28266 28267 28268
• Descriptor: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, CALCIUM ION (2 entities in total)
• Functional Keywords: pip2 degradation, ip3 production, dag production, g protein signaling, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 138870.50

Authors

Falzone, M.E.,MacKinnon, R. (deposition date: 2022-09-28, release date: 2023-05-24, Last modification date: 2024-06-19)

Primary citation

Falzone, M.E.,MacKinnon, R.
G beta gamma activates PIP2 hydrolysis by recruiting and orienting PLC beta on the membrane surface.
Proc.Natl.Acad.Sci.USA, 120:e2301121120-e2301121120, 2023

PubMed Abstract: catalyze the hydrolysis of phosphatidylinositol 4, 5-bisphosphate [Formula: see text] into [Formula: see text] [Formula: see text] and [Formula: see text]  [Formula: see text]. [Formula: see text] regulates the activity of many membrane proteins, while and lead to increased intracellular Ca levels and activate protein kinase C, respectively. are regulated by G protein-coupled receptors through direct interaction with [Formula: see text] and [Formula: see text] and are aqueous-soluble enzymes that must bind to the cell membrane to act on their lipid substrate. This study addresses the mechanism by which [Formula: see text] activates 3. We show that 3 functions as a slow Michaelis-Menten enzyme ( [Formula: see text] ) on membrane surfaces. We used membrane partitioning experiments to study the solution-membrane localization equilibrium of 3. Its partition coefficient is such that only a small quantity of 3 exists in the membrane in the absence of [Formula: see text] . When [Formula: see text] is present, equilibrium binding on the membrane surface increases 3 in the membrane, increasing [Formula: see text] in proportion. Atomic structures on membrane vesicle surfaces show that two [Formula: see text] anchor 3 with its catalytic site oriented toward the membrane surface. Taken together, the enzyme kinetic, membrane partitioning, and structural data show that [Formula: see text] activates by increasing its concentration on the membrane surface and orienting its catalytic core to engage [Formula: see text] . This principle of activation explains rapid stimulated catalysis with low background activity, which is essential to the biological processes mediated by [Formula: see text], and .

PubMed: 37172014
DOI: 10.1073/pnas.2301121120

Experimental method

ELECTRON MICROSCOPY (3.6 Å)