+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27221 | |||||||||
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タイトル | Cryo-EM map of human LIF signaling complex with full extracellular domains | |||||||||
マップデータ | LIF complex main map | |||||||||
試料 |
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キーワード | cytokine signaling / LIF / gp130 / LIFR / CYTOKINE | |||||||||
機能・相同性 | 機能・相同性情報 leukemia inhibitory factor receptor binding / spongiotrophoblast differentiation / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / meiotic nuclear division / leukemia inhibitory factor receptor activity / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / muscle organ morphogenesis / ciliary neurotrophic factor receptor activity / negative regulation of meiotic nuclear division ...leukemia inhibitory factor receptor binding / spongiotrophoblast differentiation / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / meiotic nuclear division / leukemia inhibitory factor receptor activity / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / muscle organ morphogenesis / ciliary neurotrophic factor receptor activity / negative regulation of meiotic nuclear division / leukemia inhibitory factor signaling pathway / negative regulation of interleukin-6-mediated signaling pathway / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / RUNX1 regulates transcription of genes involved in interleukin signaling / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / interleukin-6 receptor complex / regulation of metanephric nephron tubule epithelial cell differentiation / lung lobe morphogenesis / positive regulation of peptidyl-serine phosphorylation of STAT protein / trophoblast giant cell differentiation / negative regulation of hormone secretion / cell surface receptor signaling pathway via STAT / lung vasculature development / interleukin-11-mediated signaling pathway / T-helper 17 cell lineage commitment / positive regulation of adaptive immune response / positive regulation of acute inflammatory response / positive regulation of macrophage differentiation / positive regulation of astrocyte differentiation / intestinal epithelial cell development / positive regulation of platelet aggregation / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of cell adhesion mediated by integrin / cytokine receptor activity / lung alveolus development / glycogen metabolic process / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / regulation of cell differentiation / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / MAPK3 (ERK1) activation / cytokine binding / growth factor binding / Interleukin-10 signaling / MAPK1 (ERK2) activation / somatic stem cell population maintenance / macrophage differentiation / decidualization / positive regulation of vascular endothelial growth factor production / blood vessel remodeling / neuron development / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / embryo implantation / response to cytokine / cytokine activity / stem cell differentiation / growth factor activity / cell morphogenesis / negative regulation of ERK1 and ERK2 cascade / cytokine-mediated signaling pathway / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of fibroblast proliferation / positive regulation of peptidyl-serine phosphorylation / gene expression / scaffold protein binding / fibroblast proliferation / Interleukin-4 and Interleukin-13 signaling / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / receptor complex / cell surface receptor signaling pathway / response to hypoxia / immune response / membrane raft / negative regulation of cell population proliferation / external side of plasma membrane / signaling receptor binding / neuronal cell body / positive regulation of cell population proliferation / dendrite / positive regulation of gene expression / negative regulation of apoptotic process / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane 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: 3.54 Å | |||||||||
データ登録者 | Zhou Y / Franklin MC | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Sci Adv / 年: 2023 タイトル: Structural insights into the assembly of gp130 family cytokine signaling complexes. 著者: Yi Zhou / Panayiotis E Stevis / Jing Cao / Kei Saotome / Jiaxi Wu / Arielle Glatman Zaretsky / Sokol Haxhinasto / George D Yancopoulos / Andrew J Murphy / Mark W Sleeman / William C Olson / Matthew C Franklin / 要旨: The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. ...The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. We determined cryo-electron microscopy structures of five signaling complexes of this family, containing full receptor ectodomains bound to their respective ligands ciliary neurotrophic factor, cardiotrophin-like cytokine factor 1 (CLCF1), leukemia inhibitory factor, IL-27, and IL-6. Our structures collectively reveal similarities and differences in the assembly of these complexes. The acute bends at both signaling receptors in all complexes bring the membrane-proximal domains to a ~30 angstrom range but with distinct distances and orientations. We also reveal how CLCF1 engages its secretion chaperone cytokine receptor-like factor 1. Our data provide valuable insights for therapeutically targeting gp130-mediated signaling. | |||||||||
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_27221.map.gz | 229.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-27221-v30.xml emd-27221.xml | 17.4 KB 17.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_27221.png | 91.8 KB | ||
Filedesc metadata | emd-27221.cif.gz | 6.6 KB | ||
その他 | emd_27221_half_map_1.map.gz emd_27221_half_map_2.map.gz | 226.8 MB 226.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27221 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27221 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_27221_validation.pdf.gz | 1.2 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_27221_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | emd_27221_validation.xml.gz | 15.8 KB | 表示 | |
CIF形式データ | emd_27221_validation.cif.gz | 18.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27221 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27221 | HTTPS FTP |
-関連構造データ
関連構造データ | 8d6aMC 8d74C 8d7eC 8d7hC 8d7rC 8d82C 8d85C 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_27221.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | LIF complex main 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: 0.86 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
-ハーフマップ: half map A
ファイル | emd_27221_half_map_1.map | ||||||||||||
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注釈 | half map A | ||||||||||||
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 B
ファイル | emd_27221_half_map_2.map | ||||||||||||
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注釈 | half map B | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Human LIF in complex with gp130 and LIFR
全体 | 名称: Human LIF in complex with gp130 and LIFR |
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要素 |
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-超分子 #1: Human LIF in complex with gp130 and LIFR
超分子 | 名称: Human LIF in complex with gp130 and LIFR / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Leukemia inhibitory factor
分子 | 名称: Leukemia inhibitory factor / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 19.652777 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: PLPITPVNAT CAIRHPCHNN LMNQIRSQLA QLNGSANALF ILYYTAQGEP FPNNLDKLCG PNVTDFPPFH ANGTEKAKLV ELYRIVVYL GTSLGNITRD QKILNPSALS LHSKLNATAD ILRGLLSNVL CRLCSKYHVG HVDVTYGPDT SGKDVFQKKK L GCQLLGKY KQIIAVLAQA F UniProtKB: Leukemia inhibitory factor |
-分子 #2: Interleukin-6 receptor subunit beta
分子 | 名称: Interleukin-6 receptor subunit beta / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 71.233203 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
配列 | 文字列: ELLDPCGYIS PESPVVQLHS NFTAVCVLKE KCMDYFHVNA NYIVWKTNHF TIPKEQYTII NRTASSVTFT DIASLNIQLT CNILTFGQL EQNVYGITII SGLPPEKPKN LSCIVNEGKK MRCEWDGGRE THLETNFTLK SEWATHKFAD CKAKRDTPTS C TVDYSTVY ...文字列: ELLDPCGYIS PESPVVQLHS NFTAVCVLKE KCMDYFHVNA NYIVWKTNHF TIPKEQYTII NRTASSVTFT DIASLNIQLT CNILTFGQL EQNVYGITII SGLPPEKPKN LSCIVNEGKK MRCEWDGGRE THLETNFTLK SEWATHKFAD CKAKRDTPTS C TVDYSTVY FVNIEVWVEA ENALGKVTSD HINFDPVYKV KPNPPHNLSV INSEELSSIL KLTWTNPSIK SVIILKYNIQ YR TKDASTW SQIPPEDTAS TRSSFTVQDL KPFTEYVFRI RCMKEDGKGY WSDWSEEASG ITYEDRPSKA PSFWYKIDPS HTQ GYRTVQ LVWKTLPPFE ANGKILDYEV TLTRWKSHLQ NYTVNATKLT VNLTNDRYLA TLTVRNLVGK SDAAVLTIPA CDFQ ATHPV MDLKAFPKDN MLWVEWTTPR ESVKKYILEW CVLSDKAPCI TDWQQEDGTV HRTYLRGNLA ESKCYLITVT PVYAD GPGS PESIKAYLKQ APPSKGPTVR TKKVGKNEAV LEWDQLPVDV QNGFIRNYTI FYRTIIGNET AVNVDSSHTE YTLSSL TSD TLYMVRMAAY TDEGGKDGPE FTFTTPKFAQ GEIEEQKLIS EEDLGGEQKL ISEEDLHHHH HH UniProtKB: Interleukin-6 receptor subunit beta |
-分子 #3: Leukemia inhibitory factor receptor
分子 | 名称: Leukemia inhibitory factor receptor / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 92.834812 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
配列 | 文字列: QKKGAPHDLK CVTNNLQVWN CSWKAPSGTG RGTDYEVCIE NRSRSCYQLE KTSIKIPALS HGDYEITINS LHDFGSSTSK FTLNEQNVS LIPDTPEILN LSADFSTSTL YLKWNDRGSV FPHRSNVIWE IKVLRKESME LVKLVTHNTT LNGKDTLHHW S WASDMPLE ...文字列: QKKGAPHDLK CVTNNLQVWN CSWKAPSGTG RGTDYEVCIE NRSRSCYQLE KTSIKIPALS HGDYEITINS LHDFGSSTSK FTLNEQNVS LIPDTPEILN LSADFSTSTL YLKWNDRGSV FPHRSNVIWE IKVLRKESME LVKLVTHNTT LNGKDTLHHW S WASDMPLE CAIHFVEIRC YIDNLHFSGL EEWSDWSPVK NISWIPDSQT KVFPQDKVIL VGSDITFCCV SQEKVLSALI GH TNCPLIH LDGENVAIKI RNISVSASSG TNVVFTTEDN IFGTVIFAGY PPDTPQQLNC ETHDLKEIIC SWNPGRVTAL VGP RATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML PNQEIYNFTL NAHNPLGRSQ STILVNITEK VYPHTPTSFK VKDI NSTAV KLSWHLPGNF AKINFLCEIE IKKSNSVQEQ RNVTIKGVEN SSYLVALDKL NPYTLYTFRI RCSTETFWKW SKWSN KKQH LTTEASPSKG PDTWREWSSD GKNLIIYWKP LPINEANGKI LSYNVSCSSD EETQSLSEIP DPQHKAEIRL DKNDYI ISV VAKNSVGSSP PSKIASMEIP NDDLKIEQVV GMGKGILLTW HYDPNMTCDY VIKWCNSSRS EPCLMDWRKV PSNSTET VI ESDEFRPGIR YNFFLYGCRN QGYQLLRSMI GYIEELAPIV APNFTVEDTS ADSILVKWED IPVEELRGFL RGYLFYFG K GERDTSKMRV LESGRSDIKV KNITDISQKT LRIADLQGKT SYHLVLRAYT DGGVGPEKSM YVVTKENSEQ KLISEEDLG GEQKLISEED LHHHHHH UniProtKB: Leukemia inhibitory factor receptor |
-分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 5 / コピー数: 5 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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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凍結 | 凍結剤: ETHANE |
-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 BIOQUANTUM (6k x 4k) 平均電子線量: 40.0 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: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.6 µm 最小 デフォーカス(公称値): 1.4000000000000001 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.54 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 171328 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |