登録情報 データベース : EMDB / ID : EMD-28759 ダウンロードとリンクタイトル Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385 マップデータfiltered consensus map that masked out the ECD and AHD. 詳細 試料複合体 : human amylin 3 receptor in complex with Gs protein and San385 peptideリガンド : x 6種 詳細 キーワード GPCR / amylin receptor / receptor activity-modifying protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
cross-receptor inhibition within G protein-coupled receptor heterodimer / G protein-coupled receptor signaling pathway involved in heart process / adrenomedullin receptor activity / adrenomedullin receptor complex / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin receptor signaling pathway / calcitonin family receptor signaling pathway ... cross-receptor inhibition within G protein-coupled receptor heterodimer / G protein-coupled receptor signaling pathway involved in heart process / adrenomedullin receptor activity / adrenomedullin receptor complex / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin receptor signaling pathway / calcitonin family receptor signaling pathway / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor signaling pathway / calcitonin gene-related peptide receptor activity / amylin receptor 3 signaling pathway / amylin receptor 2 signaling pathway / amylin receptor 1 signaling pathway / amylin receptor signaling pathway / Calcitonin-like ligand receptors / negative regulation of ossification / response to amyloid-beta / positive regulation of receptor recycling / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / positive regulation of cAMP/PKA signal transduction / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / coreceptor activity / activation of adenylate cyclase activity / cellular response to hormone stimulus / Hedgehog 'off' state / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mRNA stability / cellular response to glucagon stimulus / positive regulation of calcium-mediated signaling / osteoclast differentiation / intracellular glucose homeostasis / ossification / response to glucocorticoid / acrosomal vesicle / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / protein localization to plasma membrane / positive regulation of protein localization to plasma membrane / cellular response to estradiol stimulus / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / intracellular protein transport / bone development / receptor internalization / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of insulin secretion / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / calcium ion transport / sensory perception of smell / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / 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 / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / protein transport / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / positive regulation of cold-induced thermogenesis 類似検索 - 分子機能 GPCR, family 2, calcitonin receptor / Receptor activity modifying protein / RAMP domain superfamily / Receptor activity modifying family / GPCR, family 2, calcitonin receptor family / 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 ... GPCR, family 2, calcitonin receptor / Receptor activity modifying protein / RAMP domain superfamily / Receptor activity modifying family / GPCR, family 2, calcitonin receptor family / 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, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 Receptor activity-modifying protein 3 / Calcitonin 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) / Lama glama (ラマ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 1.9 Å 詳細 データ登録者Cao J / Sexton PM / Wootten DL 資金援助 オーストラリア, 日本, 8件 詳細 詳細を隠すOrganization Grant number 国 Australian Research Council (ARC) IC200100052 オーストラリア National Health and Medical Research Council (NHMRC, Australia) 1120919 オーストラリア National Health and Medical Research Council (NHMRC, Australia) 1159006 オーストラリア National Health and Medical Research Council (NHMRC, Australia) 1150083 オーストラリア National Health and Medical Research Council (NHMRC, Australia) 1154434 オーストラリア National Health and Medical Research Council (NHMRC, Australia) 1155302 オーストラリア Japan Science and Technology 18069571 日本 Takeda Science Foundation 2019 Medical Research Grant 日本
引用ジャーナル : Nat Chem Biol / 年 : 2024タイトル : Structural insight into selectivity of amylin and calcitonin receptor agonists.著者: Jianjun Cao / Matthew J Belousoff / Elliot Gerrard / Radostin Danev / Madeleine M Fletcher / Emma Dal Maso / Herman Schreuder / Katrin Lorenz / Andreas Evers / Garima Tiwari / Melissa ... 著者 : Jianjun Cao / Matthew J Belousoff / Elliot Gerrard / Radostin Danev / Madeleine M Fletcher / Emma Dal Maso / Herman Schreuder / Katrin Lorenz / Andreas Evers / Garima Tiwari / Melissa Besenius / Ziyu Li / Rachel M Johnson / Denise Wootten / Patrick M Sexton / 要旨 : Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is ... Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMYR, and San45 bound to AMYR or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMYR. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects. 履歴 登録 2022年11月3日 - ヘッダ(付随情報) 公開 2023年8月2日 - マップ公開 2023年8月2日 - 更新 2024年10月23日 - 現状 2024年10月23日 処理サイト : RCSB / 状態 : 公開
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