G protein coupled receptor(GPCR & G Protein)

G protein-coupled receptors (guanine nucleotide-binding protein-coupled receptors) are a general term for a large class of membrane protein receptors. The commonality of these receptors is that they have seven transmembrane alpha helices in their steric structure, and the G-protein (bird) is present on the C-terminus of the peptide chain and on the intracellular loop connecting the 5th and 6th transmembrane helices. Binding site of a glycoside binding protein). Their main function is to transfer extracellular information into cells by interacting with G proteins. G protein-coupled receptors recognize a variety of ligands and stimuli, including hormones and neurotransmitters, chemokines, prostaglandins, proteases, biogenic amines, nucleosides, lipids, growth factors, odor molecules, and light. These receptors act as intracellular mediators and regulate complex network pathways. G-protein coupled signaling pathways include cAMP cAMP/PKA signaling pathway, Ca2+/PKC signaling pathway, Ca2+/NFAT signaling pathway, PLC signaling pathway, PTK signaling pathway, PKC/MEK signaling pathway, p43/p44MAPK signaling pathway, p38 MAP Signaling pathway, PI3K signaling pathway, NO-cGMP signaling pathway, Rho signaling pathway, NF-KappaB signaling pathway and JAK/STAT signaling pathway (Fang Y. et al., 2003). The G protein is a heterotrimer composed of three subunits of α, β, and γ, and when activated, G protein-coupled receptors interact with their homologous G-proteins. The G protein capable of activating adenylate cyclase is called Gs, and the inhibitory effect on the enzyme is called Gi. When Gs is in an inactive state, it is a heterotrimer, and the α subunit is bound to GDP. At this time, the receptor and the cyclase are also inactive; the binding of the hormone ligand to the receptor leads to a conformational change of the receptor. Exposure to the Gs binding site, the receptor and Gs diffuse on the membrane leading to the combination of the two, forming a receptor-Gs complex, Gsα subunit conformational changes, exclusion of GDP, combined with GTP activation, α subunit and thus βγ The subunit dissociates and simultaneously exposes a binding site to the cyclase; the α subunit binds to the cyclase to activate the latter, and ATP is used to generate cAMP; after a period of time, the GTPase activity on the α subunit causes binding. GTP is hydrolyzed to GDP, the subunit restores its original conformation, thereby separating it from the cyclase, the cyclase activation is terminated, and the alpha subunit is newly bound to the βγ subunit complex (Fang Y. et al., 2003). G-protein coupled receptor-mediated multiple signaling pathways are controlled by hormones, which are dynamically regulated between these pathways. At the receptor level, regulation can be achieved by inhibiting the coupling of G-protein coupled receptors to G proteins, redistribution of cell surface receptors, and degradation of receptors. In regulating these processes, two protein families, GRKs (G protein coupled receptor kinases) and inhibitory proteins, play key roles. GRKs) are a cluster of kinases associated with rapid desensitization of G-protein coupled receptors (GPCRs). Many GPCRs, such as opioid receptors, thromboxane receptors, 52 serotonin receptors, adrenergic receptors, etc., are prone to rapid decay of transduction signals when agonists continue to stimulate. This regulatory mechanism is mainly related to GRKs. GPCRs are a family of pharmacologically important proteins. Hundreds of drugs are involved in these receptor pathways, including antihistamines, tranquilizers, antidepressants, and antihypertensive drugs (Sah VP. et al., 2003).