7TMGPCR

The 7-transmembrane G protein-coupled receptor (7TMGPCR), also known as a GPCR or heptahelical receptor, is a large family of membrane proteins that play a crucial role in cellular signal transduction. These receptors are characterized by their structure, which consists of seven hydrophobic alpha-helical transmembrane domains connected by extracellular and intracellular loops, along with an extracellular N-terminus and an intracellular C-terminus. The 7TMGPCR family is one of the largest and most diverse groups of membrane receptors in eukaryotes, encompassing approximately 800 genes in the human genome.

7TMGPCRs mediate responses to a vast array of extracellular stimuli, including light, odorants, hormones, neurotransmitters, and lipids. Upon ligand binding, these receptors undergo conformational changes that activate associated G proteins (heterotrimeric GTP-binding proteins). This activation triggers downstream signaling cascades, such as the modulation of cyclic AMP (cAMP) levels, calcium mobilization, or the activation of phospholipase C, leading to diverse physiological effects. Examples of 7TMGPCRs include adrenergic receptors, muscarinic acetylcholine receptors, and rhodopsin, which are involved in regulating heart rate, muscle contraction, and vision, respectively.

The structural diversity of 7TMGPCRs allows them to recognize a wide range of ligands with high specificity. This specificity is influenced by the amino acid composition of the ligand-binding pocket, primarily formed by residues within the transmembrane helices. Mutations or dysfunctions in these receptors are linked to numerous human diseases, including cardiovascular disorders, neurological conditions, and cancer. As a result, 7TMGPCRs are major targets for therapeutic drugs, with approximately 30% of all prescribed medications acting on these receptors.

The study of 7TMGPCRs has advanced significantly through structural biology techniques, such as X-ray crystallography and cryo-electron microscopy, which have provided detailed insights into their activation mechanisms and ligand-binding properties. Ongoing research continues to uncover new therapeutic opportunities and deepen understanding of their role in health and disease.