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基本情報
登録情報 | データベース: PDB / ID: 8v2c | |||||||||||||||||||||
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タイトル | Cryo-EM structure of mouse type II OSM receptor complex: model for assembly core region | |||||||||||||||||||||
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![]() | CYTOKINE/RECEPTOR / cytokine signaling / OSM / gp130 / OSMR / CYTOKINE / CYTOKINE-RECEPTOR complex | |||||||||||||||||||||
機能・相同性 | ![]() oncostatin-M receptor binding / oncostatin-M receptor activity / meiotic nuclear division / IL-6-type cytokine receptor ligand interactions / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / Interleukin-27 signaling / leukemia inhibitory factor receptor activity / interleukin-6 receptor activity / interleukin-6 binding ...oncostatin-M receptor binding / oncostatin-M receptor activity / meiotic nuclear division / IL-6-type cytokine receptor ligand interactions / MAPK3 (ERK1) activation / MAPK1 (ERK2) activation / Interleukin-27 signaling / leukemia inhibitory factor receptor activity / interleukin-6 receptor activity / interleukin-6 binding / Interleukin-6 signaling / Interleukin-35 Signalling / oncostatin-M-mediated signaling pathway / negative regulation of meiotic nuclear division / oncostatin-M receptor complex / ciliary neurotrophic factor receptor binding / ciliary neurotrophic factor receptor complex / interleukin-6 receptor complex / interleukin-27-mediated signaling pathway / negative regulation of hormone secretion / interleukin-6 receptor binding / interleukin-11-mediated signaling pathway / regulation of Notch signaling pathway / positive regulation of astrocyte differentiation / intestinal epithelial cell development / peripheral nervous system development / cell surface receptor signaling pathway via STAT / glycogen metabolic process / interleukin-6-mediated signaling pathway / positive regulation of Notch signaling pathway / cytokine binding / behavioral response to pain / protein tyrosine kinase activator activity / positive regulation of osteoblast differentiation / positive regulation of T cell proliferation / coreceptor activity / positive regulation of apoptotic signaling pathway / cytokine activity / cytokine-mediated signaling pathway / cell body / response to heat / scaffold protein binding / negative regulation of neuron apoptotic process / cell surface receptor signaling pathway / positive regulation of MAPK cascade / immune response / membrane raft / external side of plasma membrane / neuronal cell body / positive regulation of cell population proliferation / dendrite / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / identical protein binding / plasma membrane 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | ![]() ![]() | |||||||||||||||||||||
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: 3.46 Å | |||||||||||||||||||||
![]() | Zhou, Y. / Franklin, M.C. | |||||||||||||||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes. 著者: Yi Zhou / Panayiotis E Stevis / Jing Cao / George Ehrlich / Jennifer Jones / Ashique Rafique / Mark W Sleeman / William C Olson / Matthew C Franklin / ![]() 要旨: Oncostatin M (OSM) is a unique Interleukin 6 (IL-6) family cytokine that plays pivotal roles in numerous biological events by signaling via two types of receptor complexes. While type I OSM receptor ...Oncostatin M (OSM) is a unique Interleukin 6 (IL-6) family cytokine that plays pivotal roles in numerous biological events by signaling via two types of receptor complexes. While type I OSM receptor complex is formed by glycoprotein 130 (gp130) heterodimerization with Leukemia Inhibitory Factor receptor (LIFR), type II OSM receptor complex is composed of gp130 and OSM receptor (OSMR). OSM is an important contributor to multiple inflammatory diseases and cancers while OSM inhibition has been shown to be effective at reducing symptoms, making OSM an attractive therapeutic target. Using cryogenic electron microscopy (cryo-EM), we characterize full extracellular assemblies of human type I OSM receptor complex and mouse type II OSM receptor complex. The juxtamembrane domains of both complexes are situated in close proximity due to acute bends of the receptors. The rigid N-terminal extension of OSM contributes to gp130 binding and OSM signaling. Neither glycosylation nor pro-domain cleavage of OSM affects its activity. Mutagenesis identifies multiple OSM and OSMR residues crucial for complex formation and signaling. Our data reveal the structural basis for the assemblies of both type I and type II OSM receptor complexes and provide insights for modulation of OSM signaling in therapeutics. | |||||||||||||||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 137.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 92.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 20645.201 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() | ||||||
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#2: タンパク質 | 分子量: 70033.594 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q00560 | ||||||
#3: タンパク質 | 分子量: 82357.742 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() | ||||||
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | 研究の焦点であるリガンドがあるか | N | Has protein modification | Y | |
-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 |
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試料調製
構成要素 | 名称: Mouse OSM in complex with gp130 and OSMR / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES |
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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 |
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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: ![]() |
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) |
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解析
EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.46 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 270829 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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