Heterotrimeric G protein
Encyclopedia
"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins. These proteins are activated by G protein-coupled receptor
s and are made up of alpha (α), beta (β) and gamma (γ) subunit
s, the latter two referred to as the beta-gamma complex
.
domain. There exist at least 20 different Gα subunits, which are separated into four main families. This nomenclature is based on their sequence homologies:
. Upon activation of the GPCR, the Gβγ complex is released from the Gα subunit after its GDP-GTP exchange.
s directly.
For example, the Gβγ complex, when bound to histamine
receptors, can activate phospholipase
A2. Gβγ complexes bound to muscarinic
acetylcholine
receptors, on the other hand, directly open G protein-coupled inward rectifying potassium channels
(GIRKs). They can also activate L-type calcium channels, as in H3 receptor pharmacology.
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
s and are made up of alpha (α), beta (β) and gamma (γ) subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
s, the latter two referred to as the beta-gamma complex
Beta-gamma complex
]]The beta-gamma complex is composed of the heterotrimeric G proteins Gβ and Gγ that are closely bound to one another....
.
Alpha subunits
Gα subunits consist of two domains, the GTPase domain, and the alpha-helicalAlpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
domain. There exist at least 20 different Gα subunits, which are separated into four main families. This nomenclature is based on their sequence homologies:
G-protein-family | α-subunit | Gene | Signal transduction | Use/Receptors (examples) | Effects (examples) |
Gi-family | |||||
Gi/o | αi Gi alpha subunit Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors... , αo |
GNAO1 GNAO1 Guanine nucleotide-binding protein G subunit alpha is a protein that in humans is encoded by the GNAO1 gene.-Interactions:GNAO1 has been shown to interact with RGS20, RGS19, RIC8A and RGS5.-Further reading:... , GNAI1 GNAI1 Guanine nucleotide-binding protein G, alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.-Interactions:GNAI1 has been shown to interact with GPR143, RGS14, RIC8A, S1PR1, RGS12 and RGS19.-Further reading:... , GNAI2 GNAI2 Guanine nucleotide-binding protein G, alpha-2 subunit is a protein that in humans is encoded by the GNAI2 gene.-Interactions:GNAI2 has been shown to interact with GPSM2, RIC8A, Interleukin 8 receptor, alpha, EYA2, RGS5 and MDFI.-Further reading:... , |
Inhibition of adenylate cyclase Adenylate cyclase Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell .... , opens K+-channels (via β/γ subunits), closes Ca2+-channels |
Muscarinic M2 and M4, chemokine receptors, α2-Adrenoreceptors Alpha-2 adrenergic receptor The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well... , Serotonin 5-HT1 receptors, Histamine H3 and H4, Dopamine D2-like receptors |
Smooth muscle contraction, depress neuronal activity |
Gt | αt (Transducin Transducin Transducin is a heterotrimeric G protein that is naturally expressed in vertebrate retina rods and cones .- Mechanism of action :... ) |
GNAT1 GNAT1 Guanine nucleotide-binding protein G subunit alpha-1 is a protein that in humans is encoded by the GNAT1 gene.-Further reading:... , GNAT2 GNAT2 Guanine nucleotide-binding protein G subunit alpha-2 is a protein that in humans is encoded by the GNAT2 gene.- Function :Transducin is a 3-subunit guanine nucleotide-binding protein which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha... |
Activation of phosphodiesterase Phosphodiesterase A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below... 6 |
Rhodopsin Rhodopsin Rhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,... |
Vision |
Ggust | αgust (Gustducin Gustducin Gustducin is a G protein associated with basic taste and the gustatory system. Due to its relatively recent discovery and isolation, not all is known about its nature and its associated pathways. It is known that it plays a large role in the transduction of bitter, sweet and umami stimuli and... ) |
GNAT3 Gustducin Gustducin is a G protein associated with basic taste and the gustatory system. Due to its relatively recent discovery and isolation, not all is known about its nature and its associated pathways. It is known that it plays a large role in the transduction of bitter, sweet and umami stimuli and... |
Activation of phosphodiesterase 6 | Taste receptors | Taste |
Gz | αz | GNAZ GNAZ Guanine nucleotide-binding protein G subunit alpha is a protein that in humans is encoded by the GNAZ gene.-Interactions:GNAZ has been shown to interact with EYA2, RGS20 and RGS19.-Further reading:... |
Inhibition of adenylate cyclase | ? | Maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids. |
Gs-family | |||||
Gs | αs Gs alpha subunit The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:... |
Activation of adenylate cyclase | Beta-adrenoreceptors; Serotonin 5-HT4, 5-HT6 and 5-HT7; Dopamine D1-like receptors, Histamine H2 | Increase heart rate, Smooth muscle relaxation, stimulate neuronal activity | |
Golf | αolf | GNAL GNAL Guanine nucleotide-binding protein G subunit alpha is a protein that in humans is encoded by the GNAL gene.-Further reading:... |
Activation of adenylate cyclase | olfactory receptor Olfactory receptor Olfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain... s |
Smell |
Gq-family | |||||
Gq | αq Gq alpha subunit Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway... , α11, α14, α15, α16 |
GNAQ GNAQ Guanine nucleotide-binding protein G subunit alpha is a protein that in humans is encoded by the GNAQ gene.-Interactions:GNAQ has been shown to interact with Sodium-hydrogen antiporter 3 regulator 1, RIC8A, RGS16, Beta adrenergic receptor kinase, RGS4 and Bruton's tyrosine kinase.-Further reading:... , GNA11 GNA11 Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the GNA11 gene.-Further reading:... , , |
Activation of phospholipase C Phospholipase C Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in... |
α1-Adrenoreceptors Alpha-1 adrenergic receptor The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic... , Histamine H1, Serotonin 5-HT2 receptors, Muscarinic M1 M3, and M5 |
Smooth muscle contraction, Ca2+ flux |
G12/13-family | |||||
G12/13 | α12, α13 | , | Activation of the Rho family of GTPases Rho family of GTPases The Rho family of GTPases is a family of small signaling G protein , and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants... |
Cytoskelatal functions, Smooth muscle contraction | |
Beta-gamma complex
The β and γ subunits are closely bound to one another and are referred to as the beta-gamma complexBeta-gamma complex
]]The beta-gamma complex is composed of the heterotrimeric G proteins Gβ and Gγ that are closely bound to one another....
. Upon activation of the GPCR, the Gβγ complex is released from the Gα subunit after its GDP-GTP exchange.
Function
The free Gβγ complex can act as a signaling molecule itself, by activating other second messengers or by gating ion channelIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s directly.
For example, the Gβγ complex, when bound to histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
receptors, can activate phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
A2. Gβγ complexes bound to muscarinic
Muscarine
Muscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
receptors, on the other hand, directly open G protein-coupled inward rectifying potassium channels
Inward-rectifier potassium ion channel
Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
(GIRKs). They can also activate L-type calcium channels, as in H3 receptor pharmacology.