+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8d7r | ||||||
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タイトル | Cryo-EM structure of human CLCF1 signaling complex: model containing the interaction core region | ||||||
要素 |
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キーワード | CYTOKINE / cytokine signaling / CLCF1 / CNTFR alpha / gp130 / LIFR | ||||||
機能・相同性 | 機能・相同性情報 CRLF-CLCF1 complex / CNTFR-CLCF1 complex / skeletal muscle organ development / leukemia inhibitory factor receptor activity / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / oncostatin-M receptor complex ...CRLF-CLCF1 complex / CNTFR-CLCF1 complex / skeletal muscle organ development / leukemia inhibitory factor receptor activity / oncostatin-M-mediated signaling pathway / interleukin-27 receptor activity / ciliary neurotrophic factor receptor activity / negative regulation of interleukin-6-mediated signaling pathway / leukemia inhibitory factor signaling pathway / oncostatin-M receptor complex / positive regulation of isotype switching to IgE isotypes / 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 / brainstem development / interleukin-11-mediated signaling pathway / T-helper 17 cell lineage commitment / sex differentiation / positive regulation of adaptive immune response / positive regulation of acute inflammatory response / protein tyrosine kinase activator activity / positive regulation of astrocyte differentiation / intestinal epithelial cell development / negative regulation of motor neuron apoptotic process / positive regulation of platelet aggregation / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / cytokine receptor activity / motor neuron apoptotic process / positive regulation of immunoglobulin production / extrinsic component of membrane / glycogen metabolic process / interleukin-6-mediated signaling pathway / Interleukin-6 signaling / positive regulation of Notch signaling pathway / positive regulation of cardiac muscle hypertrophy / suckling behavior / MAPK3 (ERK1) activation / growth factor binding / cytokine binding / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / positive regulation of vascular endothelial growth factor production / positive regulation of osteoblast differentiation / coreceptor activity / positive regulation of T cell proliferation / positive regulation of B cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / B cell differentiation / response to cytokine / cytokine activity / growth factor activity / cytokine-mediated signaling pathway / nervous system development / scaffold protein binding / negative regulation of neuron apoptotic process / receptor complex / cell surface receptor signaling pathway / apical plasma membrane / membrane raft / external side of plasma membrane / signaling receptor binding / neuronal cell body / positive regulation of cell population proliferation / dendrite / negative regulation of apoptotic process / signal transduction / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | ||||||
データ登録者 | Zhou, Y. / Franklin, M.C. | ||||||
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
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8d7r.cif.gz | 239.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8d7r.ent.gz | 183.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8d7r.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8d7r_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8d7r_full_validation.pdf.gz | 1.6 MB | 表示 | |
XML形式データ | 8d7r_validation.xml.gz | 47.5 KB | 表示 | |
CIF形式データ | 8d7r_validation.cif.gz | 67.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/d7/8d7r ftp://data.pdbj.org/pub/pdb/validation_reports/d7/8d7r | HTTPS FTP |
-関連構造データ
関連構造データ | 27231MC 8d6aC 8d74C 8d7eC 8d7hC 8d82C 8d85C C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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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
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 4種, 4分子 DCBA
#1: タンパク質 | 分子量: 23122.336 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CLCF1, BSF3, CLC, NNT1 / 発現宿主: Mus musculus (ハツカネズミ) / 参照: UniProt: Q9UBD9 |
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#2: タンパク質 | 分子量: 36123.570 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CNTFR / 発現宿主: Mus musculus (ハツカネズミ) / 参照: UniProt: P26992 |
#3: タンパク質 | 分子量: 92834.812 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: LIFR 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: P42702 |
#4: タンパク質 | 分子量: 71233.203 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: IL6ST 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: P40189 |
-糖 , 2種, 11分子
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: 糖 | ChemComp-NAG / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Human CLCF1 in complex with CNTFR alpha, gp130, and LIFR タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2600 nm / 最小 デフォーカス(公称値): 1400 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 92463 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 50.76 Å2 | ||||||||||||||||||||||||
拘束条件 |
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