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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||||||||
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| タイトル | Human Amylin1 Receptor in Complex with Gs and human Calcitonin Gene-Related Peptide | |||||||||||||||
マップデータ | postprocess consensus map | |||||||||||||||
試料 |
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キーワード | Amylin receptor / GPCR / RAMP3 / Calcitonin Gene-Related Peptide / MEMBRANE PROTEIN | |||||||||||||||
| 機能・相同性 | 機能・相同性情報nervous system process involved in regulation of systemic arterial blood pressure / calcitonin gene-related peptide binding / CGRP receptor complex / : / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 / amylin receptor complex 2 / calcitonin family receptor signaling pathway / amylin receptor complex 3 ...nervous system process involved in regulation of systemic arterial blood pressure / calcitonin gene-related peptide binding / CGRP receptor complex / : / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 / amylin receptor complex 2 / calcitonin family receptor signaling pathway / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor signaling pathway / positive regulation of interleukin-1 alpha production / calcitonin gene-related peptide receptor activity / amylin receptor 3 signaling pathway / amylin receptor 2 signaling pathway / negative regulation of calcium ion transport into cytosol / amylin receptor 1 signaling pathway / positive regulation of macrophage differentiation / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / vasculature development / G protein-coupled receptor internalization / endothelial cell proliferation / negative regulation of ossification / negative regulation of bone resorption / leukocyte cell-cell adhesion / negative regulation of osteoclast differentiation / positive regulation of cAMP/PKA signal transduction / response to amyloid-beta / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / regulation of cytosolic calcium ion concentration / endothelial cell migration / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / cellular response to hormone stimulus / Hedgehog 'off' state / coreceptor activity / negative regulation of blood pressure / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mRNA stability / cellular response to glucagon stimulus / regulation of insulin secretion / acrosomal vesicle / positive regulation of calcium-mediated signaling / ossification / response to glucocorticoid / osteoclast differentiation / adenylate cyclase activator activity / trans-Golgi network membrane / positive regulation of interleukin-8 production / protein localization to plasma membrane / intracellular protein transport / negative regulation of inflammatory response to antigenic stimulus / hormone activity / bone development / receptor internalization / regulation of blood pressure / platelet aggregation / G-protein beta/gamma-subunit complex binding / vasodilation / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine 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 / calcium ion transport / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / sensory perception of smell / 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 類似検索 - 分子機能 | |||||||||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | |||||||||||||||
| 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 / Wootten DL / Sexton PM | |||||||||||||||
| 資金援助 | オーストラリア, 日本, 4件
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引用 | ジャーナル: Biochemistry / 年: 2024タイトル: Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein. 著者: Jianjun Cao / Matthew J Belousoff / Radostin Danev / Arthur Christopoulos / Denise Wootten / Patrick M Sexton / ![]() 要旨: Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor ...Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor exists, the amylin (Amy) 1 receptor (AMYR), yet its involvement in the pathology of migraine is poorly understood. AMYR and CGRPR are heterodimers consisting of receptor activity-modifying protein 1 (RAMP1) with the calcitonin receptor (CTR) and the calcitonin receptor-like receptor (CLR), respectively. Here, we present the structure of AMYR in complex with CGRP and Gs protein and compare it with the reported structures of the AMYR complex with rat amylin (rAmy) and the CGRPR in complex with CGRP. Despite similar protein backbones observed within the receptors and the N- and C-termini of the two peptides bound to the AMYR complexes, they have distinct organization in the peptide midregions (the bypass motif) that is correlated with differences in the dynamics of the respective receptor extracellular domains. Moreover, divergent conformations of extracellular loop (ECL) 3, intracellular loop (ICL) 2, and ICL3 within the CTR and CLR protomers are evident when comparing the CGRP bound to the CGRPR and AMYR, which influences the binding mode of CGRP. However, the conserved interactions made by the C-terminus of CGRP to the CGRPR and AMYR are likely to account for cross-reactivity of nonpeptide CGRPR antagonists observed at AMYR, which also extends to other clinically used CGRPR blockers, including antibodies. | |||||||||||||||
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構造の表示
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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_43877.map.gz | 166.1 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-43877-v30.xml emd-43877.xml | 46.5 KB 46.5 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_43877_fsc.xml | 12.8 KB | 表示 | FSCデータファイル |
| 画像 | emd_43877.png | 18.3 KB | ||
| マスクデータ | emd_43877_msk_1.map | 178 MB | マスクマップ | |
| Filedesc metadata | emd-43877.cif.gz | 9.2 KB | ||
| その他 | emd_43877_additional_1.map.gz emd_43877_additional_2.map.gz emd_43877_additional_3.map.gz emd_43877_additional_4.map.gz emd_43877_additional_5.map.gz emd_43877_additional_6.map.gz emd_43877_additional_7.map.gz emd_43877_half_map_1.map.gz emd_43877_half_map_2.map.gz | 158.9 MB 152.4 MB 156.3 MB 141.1 MB 156.6 MB 155.6 MB 163.1 MB 141.5 MB 141.5 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-43877 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43877 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_43877_validation.pdf.gz | 1 MB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_43877_full_validation.pdf.gz | 1 MB | 表示 | |
| XML形式データ | emd_43877_validation.xml.gz | 19.9 KB | 表示 | |
| CIF形式データ | emd_43877_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-43877 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43877 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9aucMC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_43877.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 | postprocess 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 | ||||||||||||||||||||||||||||||||||||
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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
+追加マップ: postprocess map of receptor-focused refinement using auto-generated B...
+追加マップ: postprocess map from the ECD-focused refinement using B-factor (-15)
+追加マップ: sharpened map of receptor-focused refinement using manual input...
+追加マップ: unfiltered consensus map
+追加マップ: unfiltered map from the receptor-focused refinement
+追加マップ: postprocess map from the ECD-focused refinement
+追加マップ: postprocess map from the receptorTMD-focused refinement
+ハーフマップ: #2
+ハーフマップ: #1
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試料の構成要素
+全体 : Human Amylin 1 Receptor in complex with Gs and human calcitonin g...
+超分子 #1: Human Amylin 1 Receptor in complex with Gs and human calcitonin g...
+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: Receptor activity-modifying protein 1
+分子 #6: Calcitonin gene-related peptide 1
+分子 #7: Calcitonin receptor
+分子 #8: PALMITIC ACID
+分子 #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #10: CHOLESTEROL HEMISUCCINATE
+分子 #11: 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 |
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試料調製
| 濃度 | 5.8 mg/mL |
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| 緩衝液 | pH: 7.4 |
| グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: PLASMA CLEANING |
| 凍結 | 凍結剤: ETHANE |
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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) 撮影したグリッド数: 1 / 実像数: 7049 / 平均露光時間: 16.12 sec. / 平均電子線量: 71.15 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 |
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画像解析
-原子モデル構築 1
| 精密化 | 温度因子: 41 |
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| 得られたモデル | ![]() PDB-9auc: |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
オーストラリア,
日本, 4件
引用



















Z (Sec.)
Y (Row.)
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Trichoplusia ni (イラクサキンウワバ)




FIELD EMISSION GUN


