RhoA allosterically activates phospholipase Cε via its EF hands.

ABSTRACT: Phospholipase Cε (PLCε) cleaves phosphatidylinositol lipids to increase intracellular Ca²⁺ and activate protein kinase C (PKC) in response to stimulation of cell surface receptors. PLCε is activated via direct binding of small GTPases at the cytoplasmic leaflets of cellular membranes. In the cardiovascular system, the RhoA GTPase regulates PLCε to initiate a pathway that protects against ischemia/reperfusion injuries, but the underlying molecular mechanism is not known. We present here the cryo-electron microscopy (cryo-EM) reconstruction of RhoA bound to PLCε, showing that the G protein binds a unique insertion within the PLCε EF hands. Deletion of or mutations to this PLCε insertion decrease RhoA-dependent activation without impacting its regulation by other G proteins. Togeth

SUBMITTER: Ohri V 

PROVIDER: S-EPMC12475037 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature