8UQO

PLCb3-Gbg-Gaq complex on membranes

Summary for 8UQO

• Entry DOI: 10.2210/pdb8uqo/pdb
• Related: 8UQN
• EMDB information: 42475 42476
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein subunit gamma, Guanine nucleotide-binding protein G(q) subunit alpha, ... (9 entities in total)
• Functional Keywords: plcb3, gbg, gaq, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 272256.14

Authors

Falzone, M.E.,MacKinnon, R. (deposition date: 2023-10-24, release date: 2023-12-06)

Primary citation

Falzone, M.E.,MacKinnon, R.
The mechanism of G alpha q regulation of PLC beta 3 -catalyzed PIP2 hydrolysis.
Proc.Natl.Acad.Sci.USA, 120:e2315011120-e2315011120, 2023

PubMed Abstract: () enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein phosphorylation by protein kinase C, respectively. enzymes are under the control of G protein coupled receptor signaling through direct interactions with G proteins and and have been shown to be coincidence detectors for dual stimulation of and -coupled receptors. are aqueous-soluble cytoplasmic enzymes but partition onto the membrane surface to access their lipid substrate, complicating their functional and structural characterization. Using newly developed methods, we recently showed that activates by recruiting it to the membrane. Using these same methods, here we show that increases the catalytic rate constant, , of . Since stimulation of by depends on an autoinhibitory element (the X-Y linker), we propose that produces partial relief of the X-Y linker autoinhibition through an allosteric mechanism. We also determined membrane-bound structures of the and complexes, which show that these G proteins can bind simultaneously and independently of each other to regulate activity. The structures rationalize a finding in the enzyme assay, that costimulation by both G proteins follows a product rule of each independent stimulus. We conclude that baseline activity of is strongly suppressed, but the effect of G proteins, especially acting together, provides a robust stimulus upon G protein stimulation.

PubMed: 37991948
DOI: 10.1073/pnas.2315011120

Experimental method

ELECTRON MICROSCOPY (3.37 Å)