What is GPCR?
A large family of cell surface receptor that send signal to the intracellular targets by the help of intermediatory action of guanine-binding protein called G protein.
GPCR Stands for G protein coupled receptor or G protein linked receptor. However, G protein binds to the GPCR receptor and stimulates the signal transduction Hence they are to be known as GPCR.
The GPCR signal transduction is based on three essential components; A seven transmembrane helical domain proteins that is associated with plasma membrane, an effector protein that generates an intracellular secondary messenger and A guanine binding protein that activate effector proteins.
What is G protein?
A family of guanine-binding protein that acts as molecular switches inside the cells are involved in transmitting the signal from outside the cell to inside the cell.
Without G protein, the seven membrane helices cannot produce signals.
What is stimulating G protein?
When G proteins involve in the activation of enzymes like effector adenylate cyclase is called stimulating G protein(Gs)
What is primary messenger?
Primary messengers are basically a ligand that interacts with the surface of receptors firstly such as neurotransmitters, Growth stimulating hormones, Nitric oxides etc.
What is Secondary messenger?
Secondary messengers are signal molecules that is produce when stimulatory G protein interacts with effector proteins like adenylyl cyclase. Secondary messengers are.
- Cyclic adenosine monophosphate (cAMP)
- Cyclic guanosine monophosphate (cGMP)
- Inositol triphosphate (IP3)
- Diacylglyceral (DAG)
GPCR signal transduction was discovered and explored by Nobel laureates ALFRED G. GILMAN and MARTIN RODBELL. They discovered β-adrenergic(epinephrine) receptor system.
How GPCR signal transduction works?
The GPCR has seven membrane helices domains that is known as serpentine receptor or hepta-helical receptor. It is transmembrane proteins with seven hydrophobic regions residue that is snakelike heads and tails across the plasma membrane. The outside of PM is -NH2 region and inside the PM is -COOH region.
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The ligand like neurotransmitters bind to the surface of the receptor of GPCR within the PM. see figure (a).
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| Transduction of epinephrine signal:the β-adrenergic pathway. (Pic: principle of biochemistry by leninger) |
STEPS:
- It promotes the confirmational change in the receptor's intracellular domain.
- The stimulating G protein (Gs) is heterotrimeric protein with subunits α, β γ. The Gs is bounded with GDP then it doesn't produce secondary signal. Hence in this case it is off. While GTP replaces GDP and α subunit of Gs binds with effector proteins then it became active and produce secondary messenger. The βγ subunits dissociate from and go further for new.
- α subunits of Gs associate with the effector protein (Adenylyl cyclase) and activate it.
- The Cyclic adenosine monophosphate (cAMP) activates protein kinase A.
- This protein kinase A phosphorylate cellular protein and produce cellular response to the cell.
Posted by Bharrat Bhassker.
