+
データを開く
-
基本情報
| 登録情報 | ![]() | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Human adenosine A3 receptor Gi1 complex bound to adenosine | ||||||||||||
マップデータ | Consensus map | ||||||||||||
試料 |
| ||||||||||||
キーワード | G protein-coupled receptor / adenosine binding / seven transmembrane protein / MEMBRANE PROTEIN | ||||||||||||
| 機能・相同性 | 機能・相同性情報regulation of norepinephrine secretion / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / : / regulation of heart contraction / activation of adenylate cyclase activity / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration ...regulation of norepinephrine secretion / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / : / regulation of heart contraction / activation of adenylate cyclase activity / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / presynaptic modulation of chemical synaptic transmission / cellular response to forskolin / negative regulation of cell migration / regulation of mitotic spindle organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to wounding / Schaffer collateral - CA1 synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / 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 / 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 / GDP binding / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / 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 / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / ciliary basal body / G protein-coupled receptor signaling pathway / inflammatory response / negative regulation of cell population proliferation / lysosomal membrane / cell division / GTPase activity / synapse / dendrite / centrosome / GTP binding / protein-containing complex binding / nucleolus 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: 3.6 Å | ||||||||||||
データ登録者 | Zhang L / Mobbs JI / Glukhova A / Thal DM | ||||||||||||
| 資金援助 | オーストラリア, 3件
| ||||||||||||
引用 | ジャーナル: Nat Commun / 年: 2025タイトル: Molecular basis of ligand binding and receptor activation at the human A adenosine receptor. 著者: Liudi Zhang / Jesse I Mobbs / Felix M Bennetts / Hariprasad Venugopal / Anh T N Nguyen / Arthur Christopoulos / Daan van der Es / Laura H Heitman / Lauren T May / Alisa Glukhova / David M Thal / ![]() 要旨: Adenosine receptors (ARs: AAR, AAR, AAR, and AAR) are crucial therapeutic targets; however, developing selective, efficacious drugs for them remains a significant challenge. Here, we present high- ...Adenosine receptors (ARs: AAR, AAR, AAR, and AAR) are crucial therapeutic targets; however, developing selective, efficacious drugs for them remains a significant challenge. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human AAR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal an AAR activation mechanism that involves an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site. In addition, we identify a cryptic pocket that accommodates the N-iodobenzyl group of Piclidenoson through a ligand-dependent conformational change of M174. Our comprehensive structural and functional characterisation of AAR advances our understanding of adenosine receptor pharmacology and establishes a foundation for developing more selective therapeutics for various disorders, including inflammatory diseases, cancer, and glaucoma. #1: ジャーナル: Biorxiv / 年: 2025タイトル: Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor 著者: Zhang L / Mobbs JI / Bennetts FM / Venugopal H / Nguyen AT / Christopoulos A / van der Es D / Heitman LH / May LT / Glukhova A / Thal DM | ||||||||||||
| 履歴 |
|
-
構造の表示
| 添付画像 |
|---|
-
ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_47879.map.gz | 26.5 MB | EMDBマップデータ形式 | |
|---|---|---|---|---|
| ヘッダ (付随情報) | emd-47879-v30.xml emd-47879.xml | 26.8 KB 26.8 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_47879_fsc.xml | 11 KB | 表示 | FSCデータファイル |
| 画像 | emd_47879.png | 50 KB | ||
| Filedesc metadata | emd-47879.cif.gz | 7.1 KB | ||
| その他 | emd_47879_additional_1.map.gz emd_47879_additional_2.map.gz emd_47879_half_map_1.map.gz emd_47879_half_map_2.map.gz | 38.3 MB 26.3 MB 48.9 MB 48.9 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-47879 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-47879 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_47879_validation.pdf.gz | 814.4 KB | 表示 | EMDB検証レポート |
|---|---|---|---|---|
| 文書・詳細版 | emd_47879_full_validation.pdf.gz | 814 KB | 表示 | |
| XML形式データ | emd_47879_validation.xml.gz | 14.2 KB | 表示 | |
| CIF形式データ | emd_47879_validation.cif.gz | 20.3 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-47879 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-47879 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9ebhMC ![]() 9ebiC ![]() 9ehsC 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 ( |
|---|---|
| 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 |
|---|---|
| 「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_47879.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | 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: 1.03 Å | ||||||||||||||||||||||||||||||||||||
| 密度 |
| ||||||||||||||||||||||||||||||||||||
| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
|
-添付データ
-追加マップ: Additional Map
| ファイル | emd_47879_additional_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Additional Map | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-追加マップ: Receptor-focused map.
| ファイル | emd_47879_additional_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Receptor-focused map. | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-ハーフマップ: Half map A of consensus map
| ファイル | emd_47879_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Half map A of consensus map | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-ハーフマップ: Half map B of consensus map
| ファイル | emd_47879_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 注釈 | Half map B of consensus map | ||||||||||||
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-
試料の構成要素
-全体 : Human A3AR-Gi1-Gb1g2-scFv16 complex.
| 全体 | 名称: Human A3AR-Gi1-Gb1g2-scFv16 complex. |
|---|---|
| 要素 |
|
-超分子 #1: Human A3AR-Gi1-Gb1g2-scFv16 complex.
| 超分子 | 名称: Human A3AR-Gi1-Gb1g2-scFv16 complex. / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.414047 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 38.402867 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: HHHHHHGSSG SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR F LDDNQIVT ...文字列: HHHHHHGSSG SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR F LDDNQIVT SSGDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NA ICFFPNG NAFATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGH DNRVSC LGVTDDGMAV ATGSWDSFLK IWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Antibody fragment scFv16
| 分子 | 名称: Antibody fragment scFv16|Mus musculus (10090) / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 26.466486 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K |
-分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 7.729947 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFCAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: Adenosine receptor A3
| 分子 | 名称: Adenosine receptor A3 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 41.203633 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DYKDDDDAAN FTPVNGSSGN QSVRLVTSSS LEVLFQGPPN NSTALSLANV TYITMEIFIG LCAIVGNVLV ICVVKLNPSL QTTTFYFIV SLALADIAVG VLVMPLAIVV SLGITIHFYS CLFMTCLLLI FTHASIMSLL AIAVDRYLRV KLTVRYKRVT T HRRIWLAL ...文字列: DYKDDDDAAN FTPVNGSSGN QSVRLVTSSS LEVLFQGPPN NSTALSLANV TYITMEIFIG LCAIVGNVLV ICVVKLNPSL QTTTFYFIV SLALADIAVG VLVMPLAIVV SLGITIHFYS CLFMTCLLLI FTHASIMSLL AIAVDRYLRV KLTVRYKRVT T HRRIWLAL GLCWLVSFLV GLTPMFGWNM KLTSEYHRNV TFLSCQFVSV MRMDYMVYFS FLTWIFIPLV VMCAIYLDIF YI IRNKLSL NLSNSKETGA FYGREFKTAK SLFLVLFLFA LSWLPLSIIN CIIYFNGEVP QLVLYMGILL SHANSMMNPI VYA YKIKKF KETYLLILKA CVVCHPSDSL DTSIEKNSEH HHHHHHH UniProtKB: Adenosine receptor A3 |
-分子 #6: ADENOSINE
| 分子 | 名称: ADENOSINE / タイプ: ligand / ID: 6 / コピー数: 1 / 式: ADN |
|---|---|
| 分子量 | 理論値: 267.241 Da |
| Chemical component information | ![]() ChemComp-ADN: |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
|---|---|
解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
-
試料調製
| 緩衝液 | pH: 7.5 |
|---|---|
| 凍結 | 凍結剤: ETHANE |
-
電子顕微鏡法
| 顕微鏡 | FEI TALOS ARCTICA |
|---|---|
| 撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 60.0 e/Å2 |
| 電子線 | 加速電圧: 200 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: Talos Arctica / 画像提供: FEI Company |
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, 3件
引用





































Z (Sec.)
Y (Row.)
X (Col.)






















































解析
FIELD EMISSION GUN

