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基本情報
登録情報 | ![]() | ||||||||||||||||||||||||
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タイトル | Human Amylin2 Receptor in complex with Gs and salmon calcitonin peptide | ||||||||||||||||||||||||
![]() | post-processed consensus map | ||||||||||||||||||||||||
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![]() | Amylin receptor / GPCR / RAMP2 / salmon calcitonin / MEMBRANE PROTEIN | ||||||||||||||||||||||||
機能・相同性 | ![]() calcitonin receptor binding / basement membrane assembly / adrenomedullin binding / adrenomedullin receptor activity / adrenomedullin receptor complex / vascular associated smooth muscle cell development / adrenomedullin receptor signaling pathway / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 ...calcitonin receptor binding / basement membrane assembly / adrenomedullin binding / adrenomedullin receptor activity / adrenomedullin receptor complex / vascular associated smooth muscle cell development / adrenomedullin receptor signaling pathway / 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 / amylin receptor 3 signaling pathway / amylin receptor 2 signaling pathway / positive regulation of vasculogenesis / amylin receptor 1 signaling pathway / bicellular tight junction assembly / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / adherens junction assembly / negative regulation of vascular permeability / sprouting angiogenesis / negative regulation of ossification / response to amyloid-beta / positive regulation of cAMP/PKA signal transduction / PKA activation in glucagon signalling / hair follicle placode formation / cellular response to vascular endothelial growth factor stimulus / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / negative regulation of endothelial cell apoptotic process / vasculogenesis / renal water homeostasis / cellular response to hormone stimulus / response to glucocorticoid / Hedgehog 'off' state / coreceptor activity / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / clathrin-coated pit / regulation of mRNA stability / regulation of insulin secretion / cellular response to glucagon stimulus / osteoclast differentiation / positive regulation of calcium-mediated signaling / ossification / adenylate cyclase activator activity / acrosomal vesicle / trans-Golgi network membrane / 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 / G-protein beta/gamma-subunit complex binding / platelet aggregation / cognition / Olfactory 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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) / positive regulation of angiogenesis / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / calcium ion transport / 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 / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / GPER1 signaling 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | ||||||||||||||||||||||||
![]() | Cao J / Belousoff MJ | ||||||||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() 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 | ![]() | 84.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 34.5 KB 34.5 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.3 KB | 表示 | ![]() |
画像 | ![]() | 33.5 KB | ||
Filedesc metadata | ![]() | 8.2 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() | 71.1 MB 79.7 MB 82.5 MB 71.6 MB 71.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7tyyMC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 7tyxC ![]() 7tzfC 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 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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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 | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 0.82 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
-追加マップ: unfiltered consensus map
ファイル | emd_26199_additional_1.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 |
-追加マップ: post-processed map of local refinement that focused on...
ファイル | emd_26199_additional_2.map | ||||||||||||
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注釈 | post-processed map of 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: post-processed map of local refinement that focused on...
ファイル | emd_26199_additional_3.map | ||||||||||||
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注釈 | post-processed map of 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 |
-ハーフマップ: half map of the consensus map
ファイル | emd_26199_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_26199_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 |
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試料の構成要素
+全体 : Human Amylin 2 Receptor in complex with Gs and salmon calcitonin ...
+超分子 #1: Human Amylin 2 Receptor in complex with Gs and salmon calcitonin ...
+分子 #1: Receptor activity-modifying protein 2
+分子 #2: Calcitonin-1
+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: PALMITIC ACID
+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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![]() | 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 | 4 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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 |