Protein-Coupled Receptors, often abbreviated as GPCRs, are a large and diverse family of transmembrane receptors that sit on the surface of cells and play a critical role in relaying external signals into the cell’s interior. They are essential components of the endocrine system, serving as the primary docking sites for numerous hormones, neurotransmitters, and growth factors. Upon binding a ligand, GPCRs undergo a conformational change that activates an associated intracellular G-protein, initiating a complex signaling cascade that ultimately alters cellular function. Their ubiquity and central role in signaling make them major targets for pharmacological interventions.
Origin
The concept and structure of these receptors were established through decades of molecular biology research, culminating in the Nobel Prize-winning work that elucidated their signaling mechanism. The name is purely descriptive, referring to their function as receptors that couple to intracellular G-proteins. They are a foundational element of cellular communication and pharmacology.
Mechanism
The mechanism of action begins when an extracellular signaling molecule, such as a hormone like adrenaline or a gonadotropin, binds to the specific binding pocket of the GPCR. This binding induces a change in the receptor’s cytoplasmic domain, which allows it to interact with and activate a heterotrimeric G-protein. The activated G-protein then dissociates into subunits, which proceed to modulate the activity of various downstream effector enzymes or ion channels, such as adenylyl cyclase or phospholipase C. This cascade rapidly amplifies the initial hormonal signal, leading to a profound and specific change in cellular physiology.
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