+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27244 | |||||||||
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タイトル | Cryo-EM map of detergent-solubilized human IL-6 signaling complex with full extracellular domains | |||||||||
マップデータ | IL6 signaling complex main map | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 ciliary neurotrophic factor binding / positive regulation of interleukin-21 production / regulation of astrocyte activation / glucagon secretion / regulation of glucagon secretion / negative regulation of interleukin-1-mediated signaling pathway / hepatic immune response / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway ...ciliary neurotrophic factor binding / positive regulation of interleukin-21 production / regulation of astrocyte activation / glucagon secretion / regulation of glucagon secretion / negative regulation of interleukin-1-mediated signaling pathway / hepatic immune response / oncostatin-M-mediated signaling pathway / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / interleukin-27 receptor activity / regulation of vascular endothelial growth factor production / oncostatin-M receptor complex / negative regulation of primary miRNA processing / ciliary neurotrophic factor receptor binding / interleukin-11 receptor activity / interleukin-11 binding / T follicular helper cell differentiation / interleukin-6 receptor activity / interleukin-6 binding / ciliary neurotrophic factor-mediated signaling pathway / germinal center B cell differentiation / ciliary neurotrophic factor receptor complex / interleukin-27-mediated signaling pathway / regulation of microglial cell activation / interleukin-6 receptor complex / positive regulation of extracellular matrix disassembly / positive regulation of receptor signaling pathway via STAT / positive regulation of type B pancreatic cell apoptotic process / positive regulation of apoptotic DNA fragmentation / response to peptidoglycan / hepatocyte proliferation / neutrophil apoptotic process / interleukin-6 receptor binding / negative regulation of collagen biosynthetic process / positive regulation of activation of Janus kinase activity / interleukin-11-mediated signaling pathway / inflammatory response to wounding / T-helper 17 cell lineage commitment / positive regulation of T-helper 2 cell cytokine production / positive regulation of adaptive immune response / positive regulation of B cell activation / positive regulation of glomerular mesangial cell proliferation / endocrine pancreas development / negative regulation of interleukin-8 production / positive regulation of acute inflammatory response / regulation of neuroinflammatory response / vascular endothelial growth factor production / positive regulation of astrocyte differentiation / negative regulation of chemokine production / positive regulation of neuroinflammatory response / intestinal epithelial cell development / positive regulation of platelet aggregation / neutrophil mediated immunity / positive regulation of cytokine production involved in inflammatory response / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / negative regulation of bone resorption / positive regulation of leukocyte chemotaxis / positive regulation of leukocyte adhesion to vascular endothelial cell / CD163 mediating an anti-inflammatory response / cytokine receptor activity / positive regulation of immunoglobulin production / glycogen metabolic process / maintenance of blood-brain barrier / interleukin-6-mediated signaling pathway / Interleukin-6 signaling / positive regulation of Notch signaling pathway / negative regulation of fat cell differentiation / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / cytokine binding / MAPK3 (ERK1) activation / positive regulation of interleukin-17 production / growth factor binding / Interleukin-10 signaling / MAPK1 (ERK2) activation / monocyte chemotaxis / regulation of insulin secretion / positive regulation of interleukin-10 production / humoral immune response / negative regulation of lipid storage / Transcriptional Regulation by VENTX / positive regulation of vascular endothelial growth factor production / regulation of angiogenesis / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of epithelial to mesenchymal transition / extrinsic apoptotic signaling pathway / positive regulation of chemokine production / positive regulation of T cell proliferation / response to glucocorticoid / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of glial cell proliferation / positive regulation of interleukin-1 beta production / response to activity / response to cytokine / cytokine activity 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: 3.22 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_27244.map.gz | 185.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-27244-v30.xml emd-27244.xml | 16.9 KB 16.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_27244.png | 115 KB | ||
その他 | emd_27244_half_map_1.map.gz emd_27244_half_map_2.map.gz | 335.5 MB 335.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27244 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27244 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_27244_validation.pdf.gz | 1016.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_27244_full_validation.pdf.gz | 1016.1 KB | 表示 | |
XML形式データ | emd_27244_validation.xml.gz | 17.4 KB | 表示 | |
CIF形式データ | emd_27244_validation.cif.gz | 20.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27244 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27244 | HTTPS FTP |
-関連構造データ
関連構造データ | 8d82MC 8d6aC 8d74C 8d7eC 8d7hC 8d7rC 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_27244.map.gz / 形式: CCP4 / 大きさ: 361.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | IL6 signaling complex main map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.85 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 1
ファイル | emd_27244_half_map_1.map | ||||||||||||
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注釈 | Half Map 1 | ||||||||||||
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 2
ファイル | emd_27244_half_map_2.map | ||||||||||||
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注釈 | Half Map 2 | ||||||||||||
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 IL-6 in complex with IL-6R alpha and detergent-solubilized gp130
全体 | 名称: Human IL-6 in complex with IL-6R alpha and detergent-solubilized gp130 |
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要素 |
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-超分子 #1: Human IL-6 in complex with IL-6R alpha and detergent-solubilized gp130
超分子 | 名称: Human IL-6 in complex with IL-6R alpha and detergent-solubilized gp130 タイプ: complex / ID: 1 / キメラ: Yes / 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: Soluble interleukin-6 receptor subunit alpha
分子 | 名称: Soluble interleukin-6 receptor subunit alpha / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 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: 38.69432 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: LAPRRCPAQE VARGVLTSLP GDSVTLTCPG VEPEDNATVH WVLRKPAAGS HPSRWAGMGR RLLLRSVQLH DSGNYSCYRA GRPAGTVHL LVDVPPEEPQ LSCFRKSPLS NVVCEWGPRS TPSLTTKAVL LVRKFQNSPA EDFQEPCQYS QESQKFSCQL A VPEGDSSF ...文字列: LAPRRCPAQE VARGVLTSLP GDSVTLTCPG VEPEDNATVH WVLRKPAAGS HPSRWAGMGR RLLLRSVQLH DSGNYSCYRA GRPAGTVHL LVDVPPEEPQ LSCFRKSPLS NVVCEWGPRS TPSLTTKAVL LVRKFQNSPA EDFQEPCQYS QESQKFSCQL A VPEGDSSF YIVSMCVASS VGSKFSKTQT FQGCGILQPD PPANITVTAV ARNPRWLSVT WQDPHSWNSS FYRLRFELRY RA ERSKTFT TWMVKDLQHH CVIHDAWSGL RHVVQLRAQE EFGQGEWSEW SPEAMGTPWT ESRSPPAENE VSTPMGPGGE QKL ISEEDL GGEQKLISEE DLSGHHHHHH |
-分子 #2: Interleukin-6
分子 | 名称: Interleukin-6 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 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: 20.83777 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: VPPGEDSKDV AAPHRQPLTS SERIDKQIRY ILDGISALRK ETCNKSNMCE SSKEALAENN LNLPKMAEKD GCFQSGFNEE TCLVKIITG LLEFEVYLEY LQNRFESSEE QARAVQMSTK VLIQFLQKKA KNLDAITTPD PTTNASLLTK LQAQNQWLQD M TTHLILRS FKEFLQSSLR ALRQM |
-分子 #3: Interleukin-6 receptor subunit beta
分子 | 名称: Interleukin-6 receptor subunit beta / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 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: 77.085125 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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 GEIEAIVVPV CLAFLLTTLL GVLFCFNKRD LIKKHIWPNV PDPSKSH IA QWSPHTPPRH NFNSKDQMYS DGNFTDVSVV EIEAND |
-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: 18 / 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
最終 再構成 | 想定した対称性 - 点群: C2 (2回回転対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.22 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 105760 |
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初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |