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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 salmon calcitonin peptide | ||||||||||||||||||||||||
![]() | post-processed consensus map | ||||||||||||||||||||||||
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機能・相同性 | ![]() calcitonin receptor binding / calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / positive regulation of protein glycosylation / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 ...calcitonin receptor binding / calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / positive regulation of protein glycosylation / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / 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 / regulation of G protein-coupled receptor signaling pathway / negative regulation of ossification / positive regulation of protein kinase A signaling / response to amyloid-beta / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / ossification / coreceptor activity / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to glucocorticoid / cellular response to hormone stimulus / regulation of cytosolic calcium ion concentration / regulation of mRNA stability / adenylate cyclase activator activity / positive regulation of calcium-mediated signaling / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / protein localization to plasma membrane / intracellular protein transport / G-protein beta/gamma-subunit complex binding / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / receptor internalization / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / calcium ion transport / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / protein transport / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / amyloid-beta binding / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events 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 / Johnson RM / Wootten DL / Sexton PM | ||||||||||||||||||||||||
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 | ![]() | 96.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 34.6 KB 34.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.7 KB | 表示 | ![]() |
画像 | ![]() | 34.2 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 81.2 MB 90.4 MB 92.9 MB 92.4 MB 94.9 MB 81.3 MB 81.3 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 | ![]() 7tywMC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tyxC ![]() 7tyyC ![]() 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 | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.856 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_26196_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: unfiltered map of local refinement that focused on...
ファイル | emd_26196_additional_2.map | ||||||||||||
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注釈 | unfiltered map of local refinement that focused on extracellular domain 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_26196_additional_3.map | ||||||||||||
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注釈 | post-processed map of local refinement that focused on extracellular domain 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 of local refinement that focused on...
ファイル | emd_26196_additional_4.map | ||||||||||||
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注釈 | unfiltered 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_26196_additional_5.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_26196_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_26196_half_map_2.map | ||||||||||||
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注釈 | half map of the consensus map | ||||||||||||
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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 1 Receptor in complex with Gs and salmon calcitonin ...
+超分子 #1: Human Amylin 1 Receptor in complex with Gs and salmon calcitonin ...
+分子 #1: Receptor activity-modifying protein 1
+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: 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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![]() | 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 | TFS GLACIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 200 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 |