Structure and regulation of phospholipase Cβ and ε at the membrane

• Published in: Chemistry and physics of lipids 2021-03, Vol.235, p.105050-105050, Article 105050
• Main Authors: Muralidharan, Kaushik, Van Camp, Michelle M., Lyon, Angeline M.
• Format: Article
• Language: English
• Subjects: Allosteric activation; Cell Membrane - chemistry; Cell Membrane - metabolism; Diacylglycerol (DAG); Humans; Inositol-1,4,5-triphosphate (IP3); Interfacial activation; Models, Molecular; Phosphatidylinositol-4,5-bisphosphate (PIP2); Phosphoinositide Phospholipase C - chemistry; Phosphoinositide Phospholipase C - metabolism; Phospholipase C; Phospholipase C beta - chemistry; Phospholipase C beta - metabolism; Protein Conformation
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2021.105050

•Biophysical studies of phospholipase C (PLC) β and ε subfamilies reveal new insights into basal and G protein-dependent regulation.•The properties of the membrane, including its phosphatidylinositol concentration and distribution, regulate PLC function.•The membrane and G proteins coregulate PLC, as membrane association or G protein binding is insufficient for full activation.•The conformational heterogeneity of these enzymes contributes to basal activity, membrane association and G protein activation. Phospholipase C (PLC) β and ε enzymes hydrolyze phosphatidylinositol (PI) lipids in response to direct interactions with heterotrimeric G protein subunits and small GTPases, which are activated downstream of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). PI hydrolysis generates second messengers that increase the intracellular Ca2+ concentration and activate protein kinase C (PKC), thereby regulating numerous physiological processes. PLCβ and PLCε share a highly conserved core required for lipase activity, but use different strategies and structural elements to autoinhibit basal activity, bind membranes, and engage G protein activators. In this review, we discuss recent structural insights into these enzymes and the implications for how they engage membranes alone or in complex with their G protein regulators.