G-Protein Coupled Receptor Activation is the crucial initial step in a major cellular signaling pathway, where an extracellular signal, such as a peptide hormone or neurotransmitter, binds to a G-Protein Coupled Receptor (GPCR) on the cell surface. This binding event causes a conformational change in the receptor’s structure, which subsequently enables it to activate an associated intracellular G-protein. This activation is fundamental to the body’s ability to respond to a vast array of endocrine and neuroendocrine signals, governing diverse functions from metabolism to sensory perception.
Origin
The concept is a cornerstone of molecular pharmacology and signal transduction, emerging from the landmark work on second messengers and membrane receptors in the latter half of the 20th century. GPCRs are also known as seven-transmembrane receptors due to their characteristic structural motif. Activation refers to the initiation of the signaling cascade, transitioning the receptor and its coupled G-protein from an inactive to an active, signal-propagating state.
Mechanism
Upon hormone binding, the activated GPCR acts as a guanine nucleotide exchange factor (GEF), facilitating the exchange of GDP for GTP on the alpha subunit of the heterotrimeric G-protein. The binding of GTP causes the G-protein to dissociate into an active alpha subunit and a beta-gamma dimer. These activated subunits then diffuse along the inner membrane to interact with and regulate various effector enzymes or ion channels, such as adenylyl cyclase or phospholipase C, thereby propagating the hormonal signal into the cell.
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