G-protein coupled receptor

G-Protein Coupled Receptor

G-protein coupled receptors (GPCRs) are a large family of cell surface receptors that play a key role in cellular communication and signal transduction. They are involved in numerous physiological processes and are a major target for pharmaceutical drugs.

Structure

GPCRs are characterized by their seven transmembrane α-helices. These receptors span the cell membrane and have an extracellular N-terminus and an intracellular C-terminus. The seven transmembrane domains are connected by three extracellular loops and three intracellular loops.

Mechanism of Action

Upon binding of a ligand to the extracellular domain of a GPCR, a conformational change occurs in the receptor. This change allows the receptor to interact with and activate an intracellular G-protein. G-proteins are heterotrimeric, consisting of α, β, and γ subunits. Activation of the G-protein involves the exchange of GDP for GTP on the α subunit, leading to the dissociation of the α subunit from the βγ dimer.

The activated G-protein subunits can then interact with various downstream effectors, such as adenylyl cyclase, phospholipase C, or ion channels, to propagate the signal within the cell. This can result in a variety of cellular responses, depending on the specific GPCR and the cell type.

Types of G-Proteins

G-proteins are classified based on their α subunits into four main families:

• Gs - Stimulates adenylyl cyclase, increasing cAMP levels.
• Gi/o - Inhibits adenylyl cyclase, decreasing cAMP levels.
• Gq/11 - Activates phospholipase C, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG).
• G12/13 - Involved in the regulation of the cytoskeleton and cell migration.

Physiological Roles

GPCRs are involved in a wide range of physiological processes, including:

• Vision - Rhodopsin, a GPCR, is involved in the phototransduction pathway in the retina.
• Olfaction - Olfactory receptors, which are GPCRs, detect odorants in the nasal epithelium.
• Neurotransmission - Many neurotransmitter receptors, such as adrenergic and muscarinic receptors, are GPCRs.
• Immune response - Chemokine receptors, which are GPCRs, play a role in the immune system by directing the movement of immune cells.

Clinical Significance

GPCRs are a major target for drug development, with approximately 34% of all FDA-approved drugs targeting these receptors. Drugs that target GPCRs include:

• Beta-blockers, which target adrenergic receptors to treat hypertension.
• Antihistamines, which target histamine receptors to treat allergies.
• Opioids, which target opioid receptors for pain management.

Research and Development

Ongoing research aims to better understand the structure and function of GPCRs, as well as to develop new therapeutic agents that can modulate GPCR activity with greater specificity and fewer side effects.

See Also

• Signal transduction
• Receptor (biochemistry)
• Pharmacology

References

• Lefkowitz, R. J. (2004). Historical review: A brief history and personal retrospective of seven-transmembrane receptors. Trends in Pharmacological Sciences, 25(8), 413-422.
• Pierce, K. L., Premont, R. T., & Lefkowitz, R. J. (2002). Seven-transmembrane receptors. Nature Reviews Molecular Cell Biology, 3(9), 639-650.