+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7l6w | ||||||
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タイトル | SFX structure of the MyD88 TIR domain higher-order assembly | ||||||
要素 | Myeloid differentiation primary response protein MyD88 | ||||||
キーワード | PROTEIN BINDING (タンパク質) / SFX / serial femtosecond crystallography / MyD88 (MyD88) / TIR domain / higher-order assembly | ||||||
機能・相同性 | 機能・相同性情報 regulation of chemokine (C-X-C motif) ligand 1 production / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 誘導全身抵抗性 / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin ...regulation of chemokine (C-X-C motif) ligand 1 production / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 誘導全身抵抗性 / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin / toll-like receptor 8 signaling pathway / response to peptidoglycan / positive regulation of lymphocyte proliferation / positive regulation of interleukin-23 production / establishment of endothelial intestinal barrier / IRAK4 deficiency (TLR5) / regulation of neutrophil migration / MyD88 dependent cascade initiated on endosome / cellular response to oxidised low-density lipoprotein particle stimulus / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / neutrophil activation involved in immune response / interleukin-33-mediated signaling pathway / Toll-like receptor binding / microglia differentiation / RIP-mediated NFkB activation via ZBP1 / positive regulation of cytokine production involved in inflammatory response / interleukin-1 receptor binding / death receptor binding / MyD88 deficiency (TLR2/4) / positive regulation of macrophage cytokine production / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / IRAK4 deficiency (TLR2/4) / skin development / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / positive regulation of NLRP3 inflammasome complex assembly / extrinsic component of plasma membrane / type I interferon-mediated signaling pathway / defense response to protozoan / positive regulation of interleukin-17 production / response to amine / immunoglobulin mediated immune response / positive regulation of type I interferon production / response to amino acid / signaling adaptor activity / 食作用 / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / extrinsic component of cytoplasmic side of plasma membrane / response to interleukin-1 / positive regulation of interleukin-1 beta production / positive regulation of interleukin-8 production / positive regulation of JNK cascade / positive regulation of smooth muscle cell proliferation / response to organic cyclic compound / positive regulation of interleukin-6 production / Interleukin-1 signaling / cellular response to mechanical stimulus / : / positive regulation of tumor necrosis factor production / PIP3 activates AKT signaling / 遺伝子発現 / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / cellular response to lipopolysaccharide / cell surface receptor signaling pathway / molecular adaptor activity / endosome membrane / defense response to Gram-positive bacterium / defense response to bacterium / 自然免疫系 / apoptotic process / positive regulation of gene expression / 細胞膜 / シグナル伝達 / positive regulation of transcription by RNA polymerase II / protein-containing complex / identical protein binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / 自由電子レーザー / 分子置換 / 解像度: 2.3 Å | ||||||
データ登録者 | Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Flueckiger, L. / Nanson, J.D. ...Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Flueckiger, L. / Nanson, J.D. / Rahaman, M.H. / Aquila, A. / Hunter, M.S. / Liang, M. / Yoon, C.H. / Zhao, J. / Zatsepin, N.A. / Abbey, B. / Sierecki, E. / Gambin, Y. / Stacey, K.J. / Darmanin, C. / Kobe, B. / Xu, H. / Ve, T. | ||||||
資金援助 | オーストラリア, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. 著者: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D ...著者: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D Nanson / Md Habibur Rahaman / Andrew Aquila / Mark S Hunter / Mengning Liang / Chun Hong Yoon / Jingjing Zhao / Nadia A Zatsepin / Brian Abbey / Emma Sierecki / Yann Gambin / Katryn J Stacey / Connie Darmanin / Bostjan Kobe / Hongyi Xu / Thomas Ve / 要旨: MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and ...MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88 assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MAL. We demonstrate via mutagenesis that the MyD88 assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques. | ||||||
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 | 7l6w.cif.gz | 127.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7l6w.ent.gz | 98.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7l6w.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/l6/7l6w ftp://data.pdbj.org/pub/pdb/validation_reports/l6/7l6w | HTTPS FTP |
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-関連構造データ
関連構造データ | 7beqSC 7berC S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
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類似構造データ | |
実験データセット #1 | データ参照: 10.11577/1767965 / データの種類: diffraction image data |
-リンク
-集合体
登録構造単位 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 16207.992 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: MYD88 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q99836 |
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#2: 水 | ChemComp-HOH / |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1029868 |
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-試料調製
結晶 | マシュー密度: 2.31 Å3/Da / 溶媒含有率: 46.65 % |
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結晶化 | 温度: 310 K / 手法: batch mode 詳細: MAL TIR (0.5-3 micromolar) was incubated with MyD88 TIR domain (60-100 micromolar) in 10 millimolar HEPES at pH 7.5-8, 150 millimolar NaCl at 298-310K. |
-データ収集
回折 | 平均測定温度: 300 K / Ambient temp details: Room temperature / Serial crystal experiment: Y |
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放射光源 | 由来: 自由電子レーザー / サイト: SLAC LCLS / ビームライン: CXI / 波長: 1.314 Å |
検出器 | タイプ: CS-PAD CXI-1 / 検出器: PIXEL / 日付: 2015年12月17日 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1.314 Å / 相対比: 1 |
反射 | 解像度: 2.3→30.94 Å / Num. obs: 7118 / % possible obs: 95.8 % / 冗長度: 1 % / CC1/2: 0.9 / Net I/σ(I): 2.6 |
反射 シェル | 解像度: 2.3→2.38 Å / 冗長度: 1 % / Mean I/σ(I) obs: 1.1 / Num. unique obs: 560 / CC1/2: 0.36 / % possible all: 78.1 |
Serial crystallography sample delivery | 解説: GDVN / 手法: injection |
Serial crystallography sample delivery injection | Carrier solvent: buffer / Crystal conc.: 750 / Flow rate: 20 µL/min |
Serial crystallography data reduction | Frame hits: 13528 / Frames indexed: 4725 / Frames total: 1029868 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: 7BEQ 解像度: 2.3→30.94 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.894 / SU ML: 0.409 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R Free: 0.302 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 65.83 Å2 / Biso mean: 38.208 Å2 / Biso min: 19.17 Å2
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精密化ステップ | サイクル: final / 解像度: 2.3→30.94 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.3→2.36 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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精密化 TLS | 手法: refined / Origin x: 15.0932 Å / Origin y: 2.168 Å / Origin z: 11.5879 Å
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