Skip to content
Related Articles
Open in App
Not now

Related Articles

G Protein-Coupled Receptor

Improve Article
Save Article
Like Article
  • Last Updated : 04 Dec, 2022
Improve Article
Save Article
Like Article

Receptors are characterized as specific cell membrane structures. They are mostly made of proteins, which attach to ligands and trigger signaling reactions. A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific effect in the cell. In a cell or on its surface, cellular receptors are proteins that take in signals. This chemical signal occurs when a protein ligand interacts with a protein receptor during normal physiology. A cell can signal another cell or itself by releasing a chemical messenger called a ligand. The binding has biological effects that can take many different forms, such as affecting gene transcription or translation or modifying cell shape. Usually, a single ligand may attach to a single receptor and trigger a biological response. Cellular signaling can take many distinct forms, each of which requires a unique set of ligands and receptors.

Receptor Functions

Receptors are protein molecules that serve a variety of purposes in the target cell or on its surface, including:

  • It controls cell adhesion
  • It facilitates signal transduction.
  • It regulates the channels in the membrane
  • It also has a role in immunotherapy and immunological responses.
  • Cell metabolisms, such as cell growth, cell division, and cell death, are induced. G protein-coupled receptors (GPCRs) are essential membrane proteins that cells utilize to translate extracellular signals into intracellular actions. These actions include reactions to hormones, and neurotransmitters, as well as reactions to signals from the senses of sight, smell, and taste. 

On the basis of their structural and sequence similarities, these receptors can be divided into five different families, including adhesion, Frizzled/Taste2, secretin, glutamate, and rhodopsin (family A). Seven transmembranes (TM) helices coupled to three extracellular loops and three intracellular loops are common structural motifs shared by all of them. GPCRs exhibit distinctive combinations of signal-transduction capabilities involving G protein-dependent signaling pathways, as well as G protein-independent signaling pathways, and complex regulation processes, despite the fact that their structural similarities.

What is G-Protein Coupled Receptor?

G protein-coupled receptors (GPCRs), also called seven-(pass)-transmembrane domain receptors, seven-(pass)-transmembrane domain receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), are a large family of evolutionarily related proteins that are cell surface receptors that recognize molecules outside the cell and trigger cellular responses. They are known as seven-transmembrane receptors because they couple with G proteins and traverse the cell membrane seven times. Ligands can bind to the binding site within transmembrane helices or to the extracellular N-terminus and loops (such as glutamate receptors) (Rhodopsin-like family). Although a spontaneous auto-activation of an empty receptor can also be seen, they are all agonist-activated.

Only eukaryotes, including yeast, choanoflagellates, and mammals, have G protein-coupled receptors. Light-sensitive substances, smells, pheromones, hormones, and neurotransmitters are among the ligands that bind to and activate these receptors. Their sizes range from tiny molecules to peptides to big proteins. There are numerous disorders that involve G protein-coupled receptors.

G-Protein Receptor


The G protein-coupled receptors are primarily involved in two signal transduction pathways:

  • The phosphatidylinositol signal route, 
  • cAMP signal pathway.


Although the precise size of the GPCR superfamily is unknown, genome sequence analysis has predicted that at least 831 distinct human genes (or 4% of the entire protein-coding genome) contain the genes that code for them. Despite the numerous proposed classification schemes, the superfamily was traditionally split into three classes A, B, and C, with no discernible shared sequence homology between classes.

Class A, which makes up almost 85% of the GPCR genes, is by far the largest class. Over half of class A GPCRs are predicted to encode olfactory receptors, with the remaining receptors being liganded by recognized endogenous substances or being categorized as orphan receptors.

Despite the absence of sequence homology between classes, the structure and signal transduction mechanism of all GPCRs are the same. There are 19 other subgroups within the extremely big rhodopsin A group (A1-A19). Based on sequence homology and functional similarity, GPCRs may be divided into six groups using the conventional A-F system:

  1. Class A (or 1) (Rhodopsin-like)
  2. Class B (or 2) (Secretin receptor family)
  3. Class C (or 3) (Metabotropic glutamate/pheromone)
  4. Class D (or 4) (Fungal mating pheromone receptors)
  5. Class E (or 5) (Cyclic AMP receptors)
  6. Class F (or 6) (Frizzled/Smoothened)

G-Protein Structure

A transmembrane segment that crosses the lipid bilayer seven times makes up G-protein coupled receptors (hence they are also referred to as 7-transmembrane receptors). A G-protein is connected to this transmembrane area. All of the downstream actions of GPCRs are mediated by their G-protein since they lack an inherent enzyme activity or ion channel.

Alpha, beta, and gamma are the three distinct subunits that make up the heterotrimeric G-protein. GDP is affixed to the G—subunit proteins while it is dormant. Numerous signals, including neurotransmitters, hormones, ions, peptides, and even photons in the retina, can activate the hundreds of GPCRs that are present in the genome. Adrenoreceptors, muscarinic acetylcholine receptors, and opioid receptors are typical examples of GPCRs.

GPCR Signaling


Ligand-G-Protein Binding

A chemical that binds to a receptor and triggers a biological response is known as an agonist (ligand). In the case of G-protein coupled receptors, there are five key processes.

  1. The N-terminus or a binding site within the transmembrane region of the G-protein coupled receptor is where ligands bind to the extracellular part of the receptor.
  2. When an external ligand is bound, the GPCR undergoes a conformational shift that releases GDP from the G—subunit. proteins.
  3. Then, a GTP is used to replace the released GDP.
  4. The α-subunit and bound GTP separate from the transmembrane region of the GPCR and α-subunit as a result of the G-protein being activated.
  5. These α-subunits connect with the appropriate effectors to provide downstream effects, such as ion channel opening or modulation of enzyme activity.

Types of G-protein

A GPCR can contain numerous distinct kinds of G-protein, which differ according to their -subunit. Each alpha-subunit activates an enzyme, which affects the concentration of a secondary messenger by either raising or lowering it. This then affects a downstream effector, resulting in a biological reaction. These proteins’ final impact is determined by the particular cell in which it is present.


  •  Stimulates the enzyme adenylyl cyclase, which is responsible for converting ATP to cyclic AMP. The enzyme
  • Boosts the secondary messenger cAMP
  • Stimulates cAMP-dependent protein kinase (PKA) activity, which phosphorylates effector target proteins.


  • Prevents the enzyme adenylyl cyclase from catalyzing the conversion of ATP to cyclic AMP.
  • Lowers the secondary messenger cAMP
  • Prevents PKA (cAMP-dependent protein kinase) effector activation.

Gq or G11

  • Phospholipase C, which is stimulated by GQ or G11, cleaves PIP2 in the cell membrane into IP3 and DAG. The enzyme
  • Increases DAG, a secondary messenger, and IP3.
  • IP3 causes a Ca2+ outflow into the cytoplasm by opening calcium channels. – Effector
  • After DAG activates protein kinase C (PKC), it phosphorylates its intended target proteins. the effector.

Characteristics G-Protein Coupled Receptor

Role of G-proteins in cell division

G-proteins’ function in cell division G-protein subunits are involved in asymmetric cell division, as shown by genetic research in the insects C. elegans and Drosophila. Before the first cleavage in a one-cell C. elegans embryo, a complex of G- and GPR domain-containing proteins localize to the posterior cortex while the Par3/Par6/aPKC complex localizes to the anterior cortex, setting in motion a series of events that results in the generation of an anterior daughter cell that is larger than its posterior sister. The pull of the posterior spindle pole toward that direction causes the cleavage plane to move toward the posterior pole, which results in a disparity in sibling size.

Roles of G-proteins in mediating signals from receptor tyrosine kinases (RTKs)

Their contributions to RTK signaling are another illustration of G-proteins’ non-canonical activities. There are several publications suggesting that G-proteins might work in conjunction with RTKs. The mechanics, nevertheless, are not clearly described. Whether GPCRs are involved in each of these routes is unclear. Transactivation of GPCRs by RTKs has been suggested in some circumstances. More biochemical and genetic research is needed in these areas. Here, we shall give an illustration of the function of G13 in RTK-induced actin cytoskeletal rearrangement.

FAQs on GPCR Receptor

Question 1: What are G proteins used for?


Relaying signals from GPCRs, which serve as GEFs for G-proteins, is one of the key physiological roles of G-proteins. GPCRs are brought into an active conformational state by interacting with exogenous or endogenous agonists, which then affect the intracellular binding of G-proteins or arrestin proteins.

Question 2: What function do G protein-coupled receptors serve?


G protein-coupled receptors (GPCRs) are essential membrane proteins that cells utilize to translate extracellular signals into intracellular actions. These actions include reactions to hormones, and neurotransmitters, as well as reactions to signals from the senses of sight, smell, and taste.

Question 3: Do G-protein receptors cause what to happen?


When G proteins are activated, numerous second messenger systems and intracellular reactions are also activated, which results in physiological responses from tissues and organisms. GDP is coupled to the G subunit in the inactive heterotrimeric state.

Question 4: Where can I find G protein-coupled receptors?


G protein-coupled receptors (GPCRs) are seven-transmembrane proteins found in cell membranes, with their N- and C-termini situated on the exterior and interior surfaces, respectively. The extracellular environment triggers a variety of cellular responses, which are mediated by GPCRs.

Question 5: What are the names of G protein-coupled receptors?


A protein found in the cell membrane known as a G protein-coupled receptor (GPCR), also known as a seven-transmembrane receptor or heptahelical receptor, binds extracellular chemicals and relays signals from these substances to an intracellular component known as a G protein (guanine nucleotide-binding protein).

My Personal Notes arrow_drop_up
Like Article
Save Article
Related Articles

Start Your Coding Journey Now!