G Proteins

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G proteins, ( guanine nucleotide-binding proteins), are a family of proteins involved in second messenger cascades, alternating between an inactive (GDP) and active (GTP) bound state, ultimately going on to regulate downstream cell processes. G proteins are important signal transducing molecules in cells G proteins belong to the larger group of enzymes called GTPases.

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Types of G protein signaling two distinct families of proteins. Heterotrimeric G proteins, ("large" G proteins) are activated by GPCR and made up of alpha (α), beta (β), and gamma (γ) subunits. monomeric. "small" G proteins (20-25kDa). These proteins are homologous to the alpha (α) subunit found in heterotrimers, Both bind GTP and GDP and are involved in signal transduction.

• Heterotrimeric G proteins Receptor-activated G proteins are bound to the inside surface of the cell membrane. They consist of the Gα and the tightly associated Gβγ subunits. In order to associate with the inner leaflet of the plasma membrane, many G proteins and small GTPases are lipidated, that is, covalently modified with lipid extensions. They may be myristolated, palmitoylated or prenylated. Heterotrimeric G proteins share a common mode of action. Ligand binding causes activation, in response to a conformation change in the GPCR, exchange of GTP for GDP and dissociation in order to activate further proteins in the pathway. However, the specific mechanism differs between different types of G proteins. •

Activation As a ligand activates the GPCR, it induces a conformation change in the receptor that allows the receptor to function as a guanine nucleotide exchange factor (GEF) that exchanges GDP for GTP on the Gα subunit. This exchange triggers the dissociation of the Gα subunit, bound to GTP, from the Gβγ dimer and the receptor. Both Gα-GTP and Gβγ can then activate different signaling cascades (or second messenger pathways) and effector proteins, while the receptor is able to activate the next G protein.

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Termination The Gα subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic pathway activity, allowing it to re-associate with Gβγ and starting a new cycle. GTPase Activating Proteins(GAPs), which are specific for Gα subunits, act to accelerate hydrolysis and terminate the transduced signal. In some cases the effector itself may possess intrinsic GAP activity, which helps deactivate the pathway. This is true in the case of phospholipase c beta, which possesses GAP activity within its C-terminal region. an alternate form of regulation for the Gα subunit.

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Specific mechanisms Gαs – stimulates production of camp from ATP through activation of adenylate cyclase GαI – G αQ/11Gα12/13 – Gβδ-

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Diagram of G Protein cycle