+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33227 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Isoproterenol-activated dog beta3 adrenergic receptor | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
機能・相同性 | 機能・相同性情報 beta3-adrenergic receptor activity / beta-adrenergic receptor activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / serotonin binding / G protein-coupled serotonin receptor activity / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor ...beta3-adrenergic receptor activity / beta-adrenergic receptor activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / serotonin binding / G protein-coupled serotonin receptor activity / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / neurotransmitter receptor activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / PKA activation in glucagon signalling / hair follicle placode formation / intracellular transport / photoreceptor outer segment / D1 dopamine receptor binding / developmental growth / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / photoreceptor inner segment / adenylate cyclase activator activity / trans-Golgi network membrane / G-protein beta/gamma-subunit complex binding / 骨 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 血小板 / Glucagon-type ligand receptors / 認識 / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / sensory perception of smell / retina development in camera-type eye / GTPase binding / cell body / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to hypoxia 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) / Bos taurus (ウシ) / unidentified (未定義) / Canis lupus familiaris (イヌ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
データ登録者 | Shihoya W / Nureki O | |||||||||
資金援助 | 日本, 1件
| |||||||||
引用 | ジャーナル: Mol Cell / 年: 2021 タイトル: Cryo-EM structure of the β3-adrenergic receptor reveals the molecular basis of subtype selectivity. 著者: Chisae Nagiri / Kazuhiro Kobayashi / Atsuhiro Tomita / Masahiko Kato / Kan Kobayashi / Keitaro Yamashita / Tomohiro Nishizawa / Asuka Inoue / Wataru Shihoya / Osamu Nureki / 要旨: The β-adrenergic receptor (βAR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and ...The β-adrenergic receptor (βAR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and overactive bladder (OAB). Here, we report the cryogenic electron microscopy structure of the βAR-G signaling complex with the selective agonist mirabegron, a first-in-class drug for OAB. Comparison of this structure with the previously reported βAR and βAR structures reveals a receptor activation mechanism upon mirabegron binding to the orthosteric site. Notably, the narrower exosite in βAR creates a perpendicular pocket for mirabegron. Mutational analyses suggest that a combination of both the exosite shape and the amino-acid-residue substitutions defines the drug selectivity of the βAR agonists. Our findings provide a molecular basis for βAR subtype selectivity, allowing the design of more-selective agents with fewer adverse effects. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33227.map.gz | 2.3 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-33227-v30.xml emd-33227.xml | 23 KB 23 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_33227_fsc.xml | 6.9 KB | 表示 | FSCデータファイル |
画像 | emd_33227.png | 115.3 KB | ||
マスクデータ | emd_33227_msk_1.map | 12.4 MB | マスクマップ | |
その他 | emd_33227_half_map_1.map.gz emd_33227_half_map_2.map.gz | 11.2 MB 11.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33227 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33227 | HTTPS FTP |
-関連構造データ
関連構造データ | 7xjhMC 7dh5C M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_33227.map.gz / 形式: CCP4 / 大きさ: 12.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ボクセルのサイズ | X=Y=Z: 1.09526 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | emd_33227_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_33227_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_33227_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
+全体 : Dog beta3 adrenergic receptor bound to mirabegron in complex with...
+超分子 #1: Dog beta3 adrenergic receptor bound to mirabegron in complex with...
+超分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+超分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+超分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+超分子 #5: nanobody Nb35
+超分子 #6: Beta-3 adrenergic receptor
+分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Nanobody-35
+分子 #5: Beta-3 adrenergic receptor
+分子 #6: ISOPRENALINE
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 7 mg/mL |
---|---|
緩衝液 | pH: 8 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |