8UQO

PLCb3-Gbg-Gaq complex on membranes

8UQO の概要

• エントリーDOI: 10.2210/pdb8uqo/pdb
• 関連するPDBエントリー: 8UQN
• EMDBエントリー: 42475 42476
• 分子名称: 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)
• 機能のキーワード: plcb3, gbg, gaq, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 272256.14

構造登録者

Falzone, M.E.,MacKinnon, R. (登録日: 2023-10-24, 公開日: 2023-12-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.37 Å)