PLC is activated by two G-protein alpha subunits, alpha-q and alpha-11, as well as G-beta gamma subunits

This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals.

The PLCβ – G protein signaling pathway showing how the binding of an extracellular to a transmembrane GPCR will activate a G protein heterotrimer whose G α or G βγ subunits can bind to and activate PLC β.

Activated PLC β will hydrolyze PI(4,5)P₂ releasing Ins(1,4,5)P₃ into the cytosol where it diffuses to the endoplasmic reticulum (ER) causing the release of calcium ions into the cytosol. The lipid portion from PIP(4,5)P₂ hydrolysis, diacylglyercol, activates protein kinase C (PKC).

Comparison of the structure of the PH domains of the PLC-δ1 and –β2

Top left – The structure of rat PH-δ1. Top right - The structure of the human PH-β2. Bottom - The structural alignment of PH-δ1 and PH-β2 sequences showing the absence of the Ins(1,4,5)P₃ binding residues and the longer β5/β6 loop of PH-β2.

PLC-β2 binding sites on Gβγ

The region corresponding to the signal transfer regions are represented in light green whereas the general PLC-β2 binding domain are in dark blue. Additional regions found to be important for the Gβγ -activation of PLC-β2 are in light blue. The second-binding site for PLC-β2 found in the N-terminal region of Gβ are in magenta.

The Gγ subunit is colored in dark grey. The numeration of blade of the β-propeller is indicated.

A model of Gβγ activation of PLC-β2

The PH domain has an inhibitory effect on the X/Y domain through the residues 71–88 (β5/β6 loop) by maintaining the catalytic domain in a non- productive orientation.

Gβγ (by binding to the PH and X/Y domain) induces a slight conformational change allowing the X/Y domain to be correctly positioned at the membrane surface and hydrolyze the substrate.

Дата добавления: 2014-01-14