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Activation of Phospholipase C β by Gβγ and Gαq Involves C-Terminal Rearrangement to Release Autoinhibition.

Structure (London, England : 1993) (2020-05-14)
Isaac J Fisher, Meredith L Jenkins, Gregory G Tall, John E Burke, Alan V Smrcka
RESUMEN

Phospholipase C (PLC) enzymes hydrolyze phosphoinositide lipids to inositol phosphates and diacylglycerol. Direct activation of PLCβ by Gαq and/or Gβγ subunits mediates signaling by Gq and some Gi coupled G-protein-coupled receptors (GPCRs), respectively. PLCβ isoforms contain a unique C-terminal extension, consisting of proximal and distal C-terminal domains (CTDs) separated by a flexible linker. The structure of PLCβ3 bound to Gαq is known, however, for both Gαq and Gβγ; the mechanism for PLCβ activation on membranes is unknown. We examined PLCβ2 dynamics on membranes using hydrogen-deuterium exchange mass spectrometry (HDX-MS). Gβγ caused a robust increase in dynamics of the distal C-terminal domain (CTD). Gαq showed decreased deuterium incorporation at the Gαq binding site on PLCβ. In vitro Gβγ-dependent activation of PLC is inhibited by the distal CTD. The results suggest that disruption of autoinhibitory interactions with the CTD leads to increased PLCβ hydrolase activity.

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Sigma-Aldrich
decaetilenglicol monododecil éter, nonionic surfactant
Avanti
Brain PI(4,5)P2, Avanti Research - A Croda Brand
Avanti
Cerebro PI(4,5)P2, Avanti Research - A Croda Brand