タンパク質・ペプチド: Guanine nucleotide-binding protein G(i) subunit alpha-3,Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
タンパク質・ペプチド: Single-chain variable fragment 16
タンパク質・ペプチド: Nanobody 35
キーワード
Class B GPCR / glucagon-like peptide-1 receptor / G protein nucleotide exchange factor. / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
gastric inhibitory polypeptide receptor binding / gastric inhibitory peptide receptor activity / glucagon family peptide binding / digestive system development / gastric inhibitory peptide signaling pathway / glucagon receptor binding / regulation of fatty acid biosynthetic process / desensitization of G protein-coupled receptor signaling pathway / endocrine pancreas development / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) ...gastric inhibitory polypeptide receptor binding / gastric inhibitory peptide receptor activity / glucagon family peptide binding / digestive system development / gastric inhibitory peptide signaling pathway / glucagon receptor binding / regulation of fatty acid biosynthetic process / desensitization of G protein-coupled receptor signaling pathway / endocrine pancreas development / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / response to fatty acid / negative regulation of adenylate cyclase activity / response to selenium ion / positive regulation of D-glucose transmembrane transport / response to acidic pH / triglyceride homeostasis / G protein-coupled peptide receptor activity / GTP metabolic process / exploration behavior / response to lipid / response to starvation / positive regulation of cAMP/PKA signal transduction / peptide hormone binding / positive regulation of macroautophagy / PKA activation in glucagon signalling / hair follicle placode formation / response to amino acid / response to axon injury / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / response to glucose / Hedgehog 'off' state / Adenylate cyclase inhibitory pathway / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / sensory perception of pain / response to nutrient / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / adult locomotory behavior / trans-Golgi network membrane / generation of precursor metabolites and energy / female pregnancy / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / : / hormone activity / positive regulation of insulin secretion / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / memory / response to peptide hormone / G-protein beta/gamma-subunit complex binding / centriolar satellite / platelet aggregation / long-term synaptic potentiation / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / response to calcium ion / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / transmembrane signaling receptor activity / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex 類似検索 - 分子機能
Gastric inhibitory polypeptide / GPCR, family 2, gastric inhibitory polypeptide receptor / Glucagon/GIP/secretin/VIP / Peptide hormone / Glucagon / GIP / secretin / VIP family signature. / Glucagon like hormones / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. ...Gastric inhibitory polypeptide / GPCR, family 2, gastric inhibitory polypeptide receptor / Glucagon/GIP/secretin/VIP / Peptide hormone / Glucagon / GIP / secretin / VIP family signature. / Glucagon like hormones / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / G-protein alpha subunit, group I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Guanine nucleotide-binding protein G(i) subunit alpha-3 / Gastric inhibitory polypeptide / Gastric inhibitory polypeptide receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 類似検索 - 構成要素
生物種
Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) / Lama glama (ラマ)
ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: Structural determinants of dual incretin receptor agonism by tirzepatide. 著者: Bingfa Sun / Francis S Willard / Dan Feng / Jorge Alsina-Fernandez / Qi Chen / Michal Vieth / Joseph D Ho / Aaron D Showalter / Cynthia Stutsman / Liyun Ding / Todd M Suter / James D Dunbar / ...著者: Bingfa Sun / Francis S Willard / Dan Feng / Jorge Alsina-Fernandez / Qi Chen / Michal Vieth / Joseph D Ho / Aaron D Showalter / Cynthia Stutsman / Liyun Ding / Todd M Suter / James D Dunbar / John W Carpenter / Faiz Ahmad Mohammed / Eitaro Aihara / Robert A Brown / Ana B Bueno / Paul J Emmerson / Julie S Moyers / Tong Sun Kobilka / Matthew P Coghlan / Brian K Kobilka / Kyle W Sloop / 要旨: SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that ...SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist.
タンパク質・ペプチド: Guanine nucleotide-binding protein G(i) subunit alpha-3,Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
タンパク質・ペプチド: Single-chain variable fragment 16
タンパク質・ペプチド: Nanobody 35
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超分子 #1: cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bou...
超分子
名称: cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIP, trimeric G protein complex and stabilizing antibodies タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all