GPCR

Definition

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, comprising over 800 members in humans. These seven-transmembrane domain proteins detect extracellular signals (hormones, neurotransmitters, light, odors) and transduce them into intracellular responses by activating heterotrimeric G proteins. Upon ligand binding, GPCRs undergo conformational changes that catalyze GDP-GTP exchange on Gα subunits, triggering dissociation of Gα and Gβγ subunits that modulate downstream effectors like adenylyl cyclase, phospholipase C, and ion channels. GPCRs regulate virtually every physiological process and represent targets for approximately 35% of FDA-approved drugs, making them critical in drug discovery and therapeutic development.

Visualize GPCR in Nodes Bio

Researchers can map GPCR signaling cascades as multi-layered networks showing receptor-ligand interactions, G protein coupling specificity, downstream effector pathways, and transcriptional responses. Nodes Bio enables visualization of pathway crosstalk, identification of signaling bottlenecks, and comparison of tissue-specific GPCR expression patterns. Users can overlay drug target data to identify polypharmacology effects and predict off-target interactions across the GPCR family.

Example Use Case

A pharmaceutical team developing a β2-adrenergic receptor agonist for asthma uses network analysis to map the complete signaling cascade from receptor activation through Gs protein coupling to cAMP production and bronchodilation. By visualizing related GPCR pathways, they identify potential off-target effects on β1-adrenergic receptors in cardiac tissue. The network reveals shared downstream kinases that could explain adverse cardiovascular effects observed in clinical trials, prompting structure-guided design modifications to improve receptor subtype selectivity and therapeutic index.

Related Terms