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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 9auc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| タイトル | Human Amylin1 Receptor in Complex with Gs and human Calcitonin Gene-Related Peptide | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Amylin receptor / GPCR / RAMP3 / Calcitonin Gene-Related Peptide | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 / calcitonin gene-related peptide receptor activity / positive regulation of interleukin-1 alpha production / 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 / response to amyloid-beta / positive regulation of cAMP/PKA signal transduction / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / regulation of cytosolic calcium ion concentration / D1 dopamine receptor binding / intracellular transport / endothelial cell migration / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / cellular response to hormone stimulus / coreceptor activity / negative regulation of blood pressure / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mRNA stability / regulation of insulin secretion / cellular response to glucagon stimulus / positive regulation of calcium-mediated signaling / acrosomal vesicle / 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 / platelet aggregation / regulation of blood pressure / vasodilation / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / adenylate cyclase-activating G protein-coupled receptor 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / 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 / sensory perception of smell / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / calcium ion transport / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / 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 | 電子顕微鏡法 / 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, M.J. / Wootten, D.L. / Sexton, P.M. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 9auc.cif.gz | 280 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9auc.ent.gz | 215.2 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9auc.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
| その他 | その他のダウンロード |
-検証レポート
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/au/9auc ftp://data.pdbj.org/pub/pdb/validation_reports/au/9auc | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 43877MC M: このデータのモデリングに利用したマップデータ 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
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集合体
| 登録構造単位 | ![]()
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要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
| #1: タンパク質 | 分子量: 45683.434 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63092 |
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| #2: タンパク質 | 分子量: 38534.062 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62873 |
| #3: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-タンパク質 , 2種, 2分子 ER
| #5: タンパク質 | 分子量: 17066.701 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RAMP1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: O60894 |
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| #7: タンパク質 | 分子量: 58469.594 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CALCR / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P30988 |
-抗体 / タンパク質・ペプチド / 糖 , 3種, 5分子 NP

| #4: 抗体 | 分子量: 15140.742 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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| #6: タンパク質・ペプチド | 分子量: 3795.354 Da / 分子数: 1 / Fragment: residues 83-119 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P06881 |
| #9: 糖 |
-非ポリマー , 3種, 23分子 




| #8: 化合物 | ChemComp-PLM / #10: 化合物 | #11: 水 | ChemComp-HOH / | |
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-詳細
| 研究の焦点であるリガンドがあるか | Y |
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| Has protein modification | Y |
-実験情報
-実験
| 実験 | 手法: 電子顕微鏡法 |
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| EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
| 構成要素 | 名称: Human Amylin 1 Receptor in complex with Gs and human calcitonin gene-related peptide タイプ: COMPLEX / Entity ID: #1-#7 / 由来: RECOMBINANT |
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| 分子量 | 実験値: NO |
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 緩衝液 | pH: 7.4 |
| 試料 | 濃度: 5.8 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
| 急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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| 顕微鏡 | モデル: TFS KRIOS |
| 電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 500 nm |
| 撮影 | 平均露光時間: 16.12 sec. / 電子線照射量: 71.15 e/Å2 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 |
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解析
| EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 |
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| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
| 対称性 | 点対称性: C1 (非対称) |
| 3次元再構成 | 解像度: 2.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 247000 / 対称性のタイプ: POINT |
| 原子モデル構築 | B value: 41 |
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万見について




Homo sapiens (ヒト)

オーストラリア,
日本, 4件
引用
PDBj























Trichoplusia ni (イラクサキンウワバ)

FIELD EMISSION GUN