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 / 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 ...gastric inhibitory polypeptide receptor binding / gastric inhibitory peptide receptor activity / glucagon family peptide binding / 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 / G protein-coupled peptide receptor activity / GTP metabolic process / response to starvation / exploration behavior / peptide hormone binding / positive regulation of macroautophagy / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / response to glucose / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / response to axon injury / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / Adenylate cyclase inhibitory pathway / adenylate cyclase-activating adrenergic receptor signaling pathway / sensory perception of pain / response to nutrient / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / trans-Golgi network membrane / adult locomotory behavior / generation of precursor metabolites and energy / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to calcium ion / hormone activity / bone development / positive regulation of insulin secretion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet aggregation / G-protein beta/gamma-subunit complex binding / centriolar satellite / cognition / memory / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / sensory perception of smell / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / fibroblast proliferation 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 / G protein beta WD-40 repeat protein / 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. / 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