+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26136 | ||||||||||||
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タイトル | Cryo-EM structure of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||
マップデータ | 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||
試料 |
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キーワード | EBI2 / GPR183 / oxysterol / GPCR / signaling / immunity / immunocyte migration / IMMUNE SYSTEM | ||||||||||||
機能・相同性 | 機能・相同性情報 regulation of astrocyte chemotaxis / B cell activation involved in immune response / dendritic cell homeostasis / T follicular helper cell differentiation / mature B cell differentiation involved in immune response / Class A/1 (Rhodopsin-like receptors) / T cell chemotaxis / oxysterol binding / leukocyte chemotaxis / dendritic cell chemotaxis ...regulation of astrocyte chemotaxis / B cell activation involved in immune response / dendritic cell homeostasis / T follicular helper cell differentiation / mature B cell differentiation involved in immune response / Class A/1 (Rhodopsin-like receptors) / T cell chemotaxis / oxysterol binding / leukocyte chemotaxis / dendritic cell chemotaxis / humoral immune response / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / positive regulation of B cell proliferation / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / osteoclast differentiation / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / 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 / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / GPER1 signaling / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) 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 / G alpha (q) signalling events / Ras protein signal transduction / adaptive immune response / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / centrosome / synapse / protein-containing complex binding / GTP binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.12 Å | ||||||||||||
データ登録者 | Chen H / Hung W | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Structure / 年: 2022 タイトル: Structures of oxysterol sensor EBI2/GPR183, a key regulator of the immune response. 著者: Hongwen Chen / Weijiao Huang / Xiaochun Li / 要旨: Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and ...Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and antibody production during infection. Aberrant EBI2 signaling is implicated in inflammatory bowel disease, sclerosis, and infectious disease. Here, we report the cryo-EM structures of an EBI2-G signaling complex with its endogenous agonist 7α,25-OHC and that of an inactive EBI2 bound to the inverse agonist GSK682753A. These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site exposed to the lipid bilayer. Mutations within the oxysterol binding site and the Gα interface attenuate G protein signaling and abolish oxysterol-mediated cell migration indicating that G protein signaling directly involves in the oxysterol-EBI2 pathway. Together, these findings provide new insight into how EBI2 is activated by an oxysterol ligand and will facilitate the development of therapeutic approaches that target EBI2-linked diseases. | ||||||||||||
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 | emd_26136.map.gz | 82.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26136-v30.xml emd-26136.xml | 17.9 KB 17.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_26136.png | 43.3 KB | ||
Filedesc metadata | emd-26136.cif.gz | 6.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26136 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26136 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26136_validation.pdf.gz | 456 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_26136_full_validation.pdf.gz | 455.6 KB | 表示 | |
XML形式データ | emd_26136_validation.xml.gz | 6.1 KB | 表示 | |
CIF形式データ | emd_26136_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26136 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26136 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tuzMC 7tuyC 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 (文献) |
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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 |
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「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_26136.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | ||||||||||||||||||||||||||||||||||||
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: 0.833 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
-試料の構成要素
+全体 : Complex of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 with ...
+超分子 #1: Complex of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 with ...
+超分子 #2: G-protein coupled receptor 183
+超分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine ...
+超分子 #4: scFv16
+分子 #1: G-protein coupled receptor 183
+分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: scFv16
+分子 #6: (2S,4aS,4bS,7R,8S,8aS,9R,10aR)-7-[(2R,3R)-7-hydroxy-3,7-dimethylo...
-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 |
-試料調製
緩衝液 | pH: 7.5 |
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グリッド | モデル: C-flat-1.2/1.3 / 材質: GOLD / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (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: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DIFFRACTION / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.2 µm |
-画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.12 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 496394 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |