+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26208 | ||||||||||||||||||||||||
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タイトル | Human Amylin3 Receptor in complex with Gs and rat amylin peptide | ||||||||||||||||||||||||
マップデータ | post-processed consensus map | ||||||||||||||||||||||||
試料 |
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キーワード | Amylin receptor / GPCR / RAMP3 / rat amylin / MEMBRANE PROTEIN | ||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 Calcitonin-like ligand receptors / G protein-coupled receptor signaling pathway involved in heart process / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway ...Calcitonin-like ligand receptors / G protein-coupled receptor signaling pathway involved in heart process / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / positive regulation of adenylate cyclase activity / Calcitonin-like ligand receptors / negative regulation of ossification / negative regulation of bone resorption / eating behavior / positive regulation of receptor recycling / positive regulation of protein kinase A signaling / negative regulation of osteoclast differentiation / response to amyloid-beta / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / bone resorption / Hedgehog 'off' state / coreceptor activity / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to glucocorticoid / cellular response to hormone stimulus / cellular response to glucagon stimulus / regulation of mRNA stability / sensory perception of pain / adenylate cyclase activator activity / regulation of insulin secretion / positive regulation of calcium-mediated signaling / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / secretory granule / protein localization to plasma membrane / cellular response to estradiol stimulus / negative regulation of inflammatory response to antigenic stimulus / positive regulation of protein localization to plasma membrane / intracellular protein transport / bone development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / receptor internalization / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / cilium / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / platelet aggregation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / glucose metabolic process / calcium ion transport / GPER1 signaling / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of smell / G alpha (12/13) signalling events / extracellular vesicle 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) / 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: 2.4 Å | ||||||||||||||||||||||||
データ登録者 | Cao J / Belousoff MJ | ||||||||||||||||||||||||
資金援助 | オーストラリア, 日本, 7件
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引用 | ジャーナル: Science / 年: 2022 タイトル: A structural basis for amylin receptor phenotype. 著者: Jianjun Cao / Matthew J Belousoff / Yi-Lynn Liang / Rachel M Johnson / Tracy M Josephs / Madeleine M Fletcher / Arthur Christopoulos / Debbie L Hay / Radostin Danev / Denise Wootten / Patrick M Sexton / 要旨: Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual ...Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMYR with salmon CT (sCT), AMYR with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics. | ||||||||||||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_26208.map.gz | 166.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26208-v30.xml emd-26208.xml | 33.2 KB 33.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26208_fsc.xml | 12.8 KB | 表示 | FSCデータファイル |
画像 | emd_26208.png | 28.2 KB | ||
マスクデータ | emd_26208_msk_1.map | 178 MB | マスクマップ | |
Filedesc metadata | emd-26208.cif.gz | 7.6 KB | ||
その他 | emd_26208_additional_1.map.gz emd_26208_additional_2.map.gz emd_26208_additional_3.map.gz emd_26208_additional_4.map.gz emd_26208_half_map_1.map.gz emd_26208_half_map_2.map.gz | 166.5 MB 161.7 MB 159.3 MB 141.5 MB 141.8 MB 141.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26208 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26208 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26208_validation.pdf.gz | 1.1 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_26208_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | emd_26208_validation.xml.gz | 20 KB | 表示 | |
CIF形式データ | emd_26208_validation.cif.gz | 26.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26208 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26208 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tzfMC 7tyfC 7tyhC 7tyiC 7tylC 7tynC 7tyoC 7tywC 7tyxC 7tyyC 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) |
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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 |
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「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_26208.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | post-processed consensus map | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.65 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_26208_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: the combined map that samples the consensus map...
ファイル | emd_26208_additional_1.map | ||||||||||||
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注釈 | the combined map that samples the consensus map and the local refined map. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: post-processed map from local refinement that focused on...
ファイル | emd_26208_additional_2.map | ||||||||||||
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注釈 | post-processed map from local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: unfiltered map from local refinement that focused on...
ファイル | emd_26208_additional_3.map | ||||||||||||
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注釈 | unfiltered map from local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: unfiltered consensus map
ファイル | emd_26208_additional_4.map | ||||||||||||
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注釈 | unfiltered consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map of the consensus map
ファイル | emd_26208_half_map_1.map | ||||||||||||
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注釈 | half map of the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map of the consensus map
ファイル | emd_26208_half_map_2.map | ||||||||||||
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注釈 | half map of the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Human Amylin 3 Receptor in complex with Gs and rat amylin peptide
+超分子 #1: Human Amylin 3 Receptor in complex with Gs and rat amylin peptide
+分子 #1: Receptor activity-modifying protein 3
+分子 #2: amylin peptide
+分子 #3: Calcitonin receptor
+分子 #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #7: nanobody 35
+分子 #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #9: (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl...
+分子 #10: PALMITIC ACID
+分子 #11: CHOLESTEROL HEMISUCCINATE
+分子 #12: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 4 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 52.8 e/Å2 |
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 FIELD / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |